Volume 12, Issue 1

Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

Background In cancer, kappa B-interacting protein ( IKBIP ) has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at the transcriptional level. Methods We selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptional data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. Results We found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in isocitrate dehydrogenase (IDH) wild type and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell–substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent gene set enrichment analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed gene set variation analysis to screen the EMT-related signaling pathways and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-β pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients. Conclusions IKBIP was associated with more aggressive phenotypes of gliomas. Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.

Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

Objectives The aim of this study was to evaluate the value and long-term effect of laminectomy or laminoplasty in spinal cord tumor surgery. Patients and methods Patients with spinal cord tumor treated in Department of Neurosurgery from January 2016 to October 2019 were included in this study. Posterior median approach tumor resection was preceded in 94 cases. Vertebral plate and ligament composite replant (laminoplasty group) was proceeded in 34 cases, and vertebral plate resection (laminectomy group) was proceeded in 60 cases. All patients were followed up and neurological function imagings were conducted 1 week, 3 months, and 6 months postsurgery to evaluate the surgical efficiency and spinal stability. Results Total resection was achieved in 84 patients (89.0%); subtotal resection was achieved in 10 patients (11%). There was no significant difference between thelaminectomy group and laminoplasty group in terms of operative time, surgical site, infection rate, cerebrospinal fluid (CSF) infection, CSF leak, and length of hospitalization ( P > 0.05). The incidence of postoperative spinal deformity was 15.0% in the laminectomy group and 11.7% in the laminoplasty group ( P > 0.05). Laminoplasty vs laminectomy was associated with a similar risk of progressive deformity. However, for the cervical patients, there is significant difference ( P < 0.05) in the spinal deformity. For the patients with incision vertebral segments >3, there is no significant difference in the spinal deformity ( P > 0.05). Bone fusion was achieved in 7 (20%) patients in the laminoplasty group. Laminoplasty vs laminectomy was associated with a similar risk of progressive deformity. Conclusion Vertebral plate and ligament composite replant is a simple and practical method in spinal cord tumor surgery. Neither every case got bone fusion nor positive results turned out in survival analysis, but it is still valuable in reducing spinal deformity, especially in cervical vertebra spinal cord tumor surgery.

Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients ( n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N -cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.

This study investigated dietary supplementation as a prophylactic for neuroinflammation following traumatic brain injury (TBI) in a preclinical model. Adult male Sprague-Dawley rats received 30 days of supplementation with either water or two dietary supplements. The first consisted of high-dose omega-3 fatty acid (O3FA) (supplement A) along with vitamin D3 and vitamin E. The second had the same ingredients at different doses with an addition of cannabidiol (supplement B). Rats were subjected to an impact TBI and then euthanized 7 days post-injury and neuroinflammation quantified by histological detection of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and CD68, a marker of microglial activity. There was a trend toward increased GFAP staining in injured, unsupplemented animals as compared to sham, unsupplemented animals, consistent with increased activation of astrocytes in response to trauma which was reversed by supplement A but not by supplement B. The pattern of CD68 staining across groups was similar to that of GFAP staining. There was a trend toward an increase in the injured unsupplemented group, relative to sham which was reversed by supplement A but not by supplement B. CD68 staining in injured animals was concentrated in the perivascular domain. The consistency between trends across different measures of neuroinflammation showing benefits of high-dose O3FA supplementation following TBI suggests that the observed effects are real. These findings are preliminary, but they justify further study to determine the functional benefits associated with improvements in histological outcomes and understand associated dose-response curves.

Alzheimer’s disease (AD), the most common type of dementia, is a neurodegenerative disorder with a hidden onset, including difficult early detection and diagnosis. Nevertheless, the new crucial biomarkers for the diagnosis and pathogenesis of AD need to be explored further. Here, the common differentially expressed genes (DEGs) were identified through a comprehensive analysis of gene expression profiles from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these DEGs were mainly associated with biological processes, cellular components, and molecular functions, which are involved in multiple cellular functions. Next, we found that 9 of the 24 genes showed the same regulatory changes in the blood of patients with AD compared to those in the GEO database, and 2 of the 24 genes showed a significant correlation with Montreal Cognitive Assessment scores. Finally, we determined that mice with AD and elderly mice had the same regulatory changes in the identified DEGs in both the blood and hippocampus. Our study identified several potential core biomarkers of AD and aging, which could contribute to the early detection, differential diagnosis, treatment, and pathological analysis of AD.

Background Spinal cord injury (SCI) is the most serious complication of spinal injury, often leading to severe dysfunction of the limbs below the injured segment. Conventional therapy approaches are becoming less and less effective, and gene therapy is a new research direction by now. Methods The Sprague-Dawley rats were haphazardly assigned to two groups, namely sham group and SCI model group, and lncRNA H19 and miR-370-3p levels were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Correlation between lncRNA H19 and miR-370-3p was ascertained by luciferase report assay and RT-qPCR. After transfection with si-H19, miR-370-3p inhibitor, negative controls (NC), or both, primary spinal neurons were subjected to the simulation of lipopolysaccharide (LPS) for inducing in vitro model of SCI. Cell viability, apoptotic rate, caspase-3 activity, Bax and Bcl-2 protein, ROS generation, TNF-α, IL-1β, and IL-6 protein, as well as IκBα and p65 phosphorylation ratio were evaluated adopting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), apoptosis, caspase-3 activity, ROS generation, and western blot assays, thereby searching for the specific action mechanism on LPS-induced spinal never injury. Results SCI resulted in lncRNA H19 higher expression and miR-370-3p lower expression. LPS simulation raised a series of cellular biological changes, such as decreased viability, promoted apoptosis, generated ROS, and released inflammatory factors. lncRNA H19 inhibition reversed above LPS-induced changes. Besides, as the downstream target of lncRNA H19, miR-370-3p was oppositely regulated by lncRNA H19. The above biological changes induced by lncRNA H19 inhibition were reversed by miR-370-3p upregulation. Moreover, lncRNA H19 inhibition could block NF-κB pathway through miR-370-3p upregulation. Conclusion Inhibition of lncRNA H19/miR-370-3p mitigated spinal neuron apoptosis in an in vitro model of SCI. This provided the possibility for clinical use of gene therapy.

Background Owing to neurite promoting, antioxidant and anti-inflammatory effects of Euxanthone (Eux), the investigation was aimed to probe the neuroprotective efficacy of Eux against traumatic spinal cord injury (t-SCI) in rats and whether Eux can improve neuropathic function in t-SCI. Method Sprague-Dawley (SD) rats were randomized in – Sham, t-SCI, Eux30, and Eux60 (t-SCI + 30 and 60 mg/kg respectively). Animals with compression force-induced t-SCI were subjected to estimation of locomotor functions. Spinal cord water content and Evans blue (EB) effusion were determined for quantifying edema and intactness of the spinal cord. Oxidative stress and immunochemical markers were quantified by ELISA and western blotting. Results Findings revealed that Eux60 group animals had greater Basso, Beattie, and Bresnahan (BBB) and (incline plane test) IPT score indicating improved locomotor functions. There was a reduction in the spinal edema and water content after Eux treatment, together with lowering of oxidative stress markers. The expression of IL-6, IL-12, IL-1β, caspase-3, RANKL, TLR4, NF-κB, p-38, PI3K, and Akt in spinal cord tissues of t-SCI-induced rats was lowered after Eux treatment. Conclusion Overall, the investigation advocates that Eux attenuates t-SCI and associated inflammation, oxidative damage, and resulting apoptosis via modulation of TLR4/NF-κB/p38 and PI3K/Akt signaling cascade.

In oncogenesis and development of malignant tumor, microRNAs (miRNAs) regulate the complex gene expression associated with the tumor pathogenesis. Currently, only few studies have been conducted to identify miRNAs and the potential pathways involved in the pathogenesis of brain metastasis in patients who underwent radiotherapy, especially miRNAs in the plasma exosomes. Therefore, this study is aimed to use small RNA analysis to identify miRNAs and their potential target genes in plasma exosomes during the initiation and development of brain metastasis in patients who underwent radiotherapy. Using high-throughput sequencing technologies, we identified 35 differentially expressed miRNAs in patients with brain metastasis who had undergone radiotherapy. In annotation of miRNA targets, gene ontology enrichment analysis revealed that the targets of the differentially expressed miRNAs were significantly enriched in the regulation of cellular processes. Kyoto Encyclopedia of Genes and Genomes revealed that most of the miRNA targets were cancer-related, including genes involved in the mitogen-activated protein kinase signaling pathway, cancer-related pathways, phosphatidylinositol 3-kinase-protein kinase B signaling pathway, microtubule-associated protein kinase signaling pathway, Ras signaling pathway, regulation of the actin cytoskeleton, and axon guidance. In conclusion, this study provides a new perspective to understand the possible function of these miRNAs in the pathogenesis of brain metastasis. This was the first time that a pilot study identified plasma exosomal miRNAs in five patients with brain metastasis before and after radiotherapy. This study is the beginning; more specimen and further research are needed to explore the functional role of specific miRNAs and their potential as therapeutic targets for brain metastasis.

Objective Our previous in vivo study found that resveratrol (Res), which is a phytoalexin, attenuated 6-hydroxydopamine (6-OHDA)-induced motor dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. Therefore, we further explored the protective effect of Res on 6-OHDA-induced damage to PC12 cells in vitro with respect to the PI3K/Akt signaling pathway. Methods We incubated PC12 cells with 75 μM 6-OHDA for 24 h, and Res was then added at a final concentration of 25 μM; the protective effect was examined via MTT and lactate dehydrogenase (LDH) assays. In addition, the PI3K inhibitor LY294002 was used to investigate the potential mechanism. JC-1 staining was used to detect the mitochondrial membrane potential (MMP), and western blotting (WB) was used to detect the phosphorylation of Akt-Ser473. Results Compared with that in the control, the cell viability, total superoxide dismutase (SOD) activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly decreased, while the leakage rate of LDH was increased. And after treatment with 25 μM Res, the cell viability, total SOD activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly increased compared with those of the control cells, while the leakage rate of LDH was decreased. These effects of Res were antagonized by LY294002. Conclusions Res ameliorates 6-OHDA-induced damage to PC12 cells via activation of the PI3K/Akt signaling pathway.

Objective This study aimed to determine the safety and effectiveness of DTI-assisted neuroendoscopy for treating intracranial hemorrhage (ICH). Methods This retrospective study included clinical data from 260 patients with spontaneous supratentorial ICH who received neuroendoscopic hematoma removal. Patients were separated into groups based on the surgery method they received: DTI-assisted neuroendoscopy (69 cases) and standard neuroendoscopy (191 cases). All patients were followed up for 6 months. Multivariate logistic regression analyzed the risk factors affecting the prognosis of patients. The outcomes of the two groups were compared using Kaplan–Meier survival curves. Results The prognostic modified Rankin Scale (mRS) score was significantly better ( P = 0.027) in the DTI-assisted neuroendoscopy group than in the standard neuroendoscopy group. Logistic regression analysis showed that DTI-assisted neuroendoscopy is an independent protective factor for a favorable outcome (model 1: odds ratio [OR] = 0.42, P = 0.015; model 2: OR = 0.40, P = 0.013). Kaplan–Meier survival curves were used to show that the median time for a favorable outcome was 66 days (95% confidence interval [CI] = 48.50–83.50 days) in the DTI-assisted neuroendoscopy group and 104 days (95% CI = 75.55–132.45 days) in the standard neuroendoscopy group. Log-rank testing showed that the DTI-assisted neuroendoscopy group had a lower pulmonary infection rate ( χ 2 = 4.706, P = 0.030) and a better prognosis ( χ 2 = 5.223, P = 0.022) than the standard neuroendoscopy group. The survival rate did not differ significantly between the DTI-assisted neuroendoscopy group and the standard neuroendoscopy group ( P > 0.05). Conclusions The use of DTI in neuroendoscopic hematoma removal can significantly improve neurological function outcomes in patients, but it does not significantly affect the mortality of patients.

Background To investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice. Methods In the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress. Results Decreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions. Conclusion This work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.

Objective This investigation was carried out with an aim of exploring neuroprotection by naringin (Nar) in rats with cerebral ischemia-reperfusion (CI/R) injury and its mechanism. Methods Rats were grouped into ischemia-reperfusion (I/R), sham operation (Sham), nimodipine control (NIM), and different doses of Nar (Nar-L, Nar-M, Nar-H) groups. With Zea Longa score for assessment of neurological deficits, dry and wet method for measurement of brain tissue water content, and (2,3,5-triphenyltetrazolium chloride) TTC staining for determination of cerebral infarction volume, the related parameters were obtained and compared. Subsequently, ELISA was introduced to detect levels of proinflammatory cytokines (TNF-α, IL-8) and anti-inflammatory cytokine (IL-10) in the serum as well as superoxide dismutase (SOD) and malondialdehyde (MDA) activities in brain tissue. Western blot was applied to evaluate endoplasmic reticulum stress (ERS)-related proteins expression, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12, and activating transcription factor 6 (ATF-6). Results Nar significantly alleviated nerve injury and decreased brain tissue water content and brain infraction volume in CI/R injury rats in a concentration-dependent manner. Reduction of TNF-α, IL-8 as well as MDA content and elevation of IL-10 as well as SOD activity were confirmed to be caused by Nar treatment in a concentration-dependent manner. Meanwhile, ERS-related proteins also markedly decreased in the Nar groups. Conclusion Nar may achieve neuroprotection and alleviation of CI/R injury by anti-inflammation, anti-oxidation, and inhibiting ERS, and its efficacy is concentration-dependent.

Background To observe the therapeutic effect of conventional decompressive craniectomy with hematoma evacuation and frame-based stereotactic minimally invasive surgery (MIS) for supratentorial intracranial hematoma with herniation. Methods One hundred forty-nine patients with hypertensive ICH complicated with tentorial herniation were reviewed and analyzed in the present study. The intracranial hematoma was evacuated by emergency surgery within 6 h after admission. According to the authorized representatives’ wishes and consent, 74 of the 149 patients were treated by conventional decompressive craniectomy followed by hematoma removal, defined as the CDC group, and the remaining 75 patients underwent frame-based stereotactic MIS for ICH evacuation, defined as the MIS group. The intervals between the admission to surgery, the duration of surgery, the amount of iatrogenic bleeding, the occurrence of postoperative rebleeding, and the recovery of neurological functions were compared between the two groups. All patients were followed up for 3 months. Secondary epilepsy, survival in a vegetative state, severe pulmonary complications, mortality, and activities of daily living (ADL) classification were also recorded and compared. Results The interval between admission and surgery, the duration of surgery, and intraoperative blood loss in the MIS group were significantly decreased compared to the CDC group. The mortality rate, the rate of rebleeding, prevalence of vegetative state, and severe pulmonary complications in the MIS group were remarkably decreased compared to the CDC group. In the MIS group, the survivors’ (ADL) grade also showed advantages. Conclusions In the surgical treatment of hypertensive ICH complicated with tentorial herniation, frame-based stereotactic MIS for ICH showed advantages compared to conventional open surgery.

Background This study aimed to explore the role of miR-380-5p in cerebral ischemia/reperfusion (CIR) injury-induced neuronal cell death and the potential signaling pathway involved. Methodology Human neuroblastoma cell line SH-SY5Y cells were used in this study. Oxygen and glucose deprivation/reperfusion (OGD/R) model was used to mimic ischemia/reperfusion injury. CCK-8 assay and flow cytometry were used to examine cell survival. Quantitative real time PCR (RT-qPCR) assay and Western blotting were used to measure the change of RNA and protein expression, respectively. TargetScan and Luciferase assay was used to confirm the target of miR-380-5p. Malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured using commercial kits. Results miR-380-5p was downregulated in SH-SY5Y cells after OGD/R. Cell viability was increased by miR-380-5p, while cell apoptosis was reduced by miR-380-5p mimics. MDA was reduced by miR-380-5p mimics, while SOD and GSHPx were increased by miR-380-5p. Results of TargetScan and luciferase assay have showed that BACH1 is the direct target of miR-380-5p. Expression of NRF2 was upregulated after OGD/R, but was not affected by miR-380-5p. mRNA expression of HO-1 and NQO1 and ARE activity were increased by miR-380-5p. Overexpression of BACH1 reversed the antioxidant and neuroprotective effects of miR-380-5p. Conclusion miR-380-5p inhibited cell death induced by CIR injury through target BACH1 which also facilitated the activation of NRF2, indicating the antioxidant and neuroprotective effects of miR-380-5p.

Objectives Parkinson’s disease (PD) is a kind of common neurodegenerative disease in the world. Previous studies have proved that nervonic acid (NA), extracted from Xanthoceras sorbifolia Bunge, has the potentials of neuroprotection. However, the effect of NA on the PD remained unknown. This study was designed to investigate the NA’s potential function and relative mechanism on motor disorder. Methods 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used for producing parkinsonism motor disorder on male C57BL/6 mice. Toxicity experiments and behavioral assay were performed to evaluate the effect of NA. Besides, the expression levels of tyrosine hydroxylase and α-synuclein, as well as striatal dopamine (DA), serotonin, and their metabolites were explored through immunoblotting and chromatography after NA treatment in vivo . Results We found that NA could alleviate the MPTP-induced behavioral deficits dose-dependently. Moreover, NA has no toxic effects on the mouse liver and kidney. Of note, we found that NA significantly reduced the impact of MPTP impairment and striatal DA, serotonin, and metabolites were remained unaffected. In addition, tyrosine hydroxylase was upregulated while α-synuclein being downregulated and the oxidative stress was partially repressed evidenced by the upregulation of superoxide dismutase and glutathione activity after NA treatment. Conclusion Our findings unveil NA’s potential for protecting motor system against motor disorder in the PD mouse model without any side effects, indicating NA as an alternative strategy for PD symptom remission.

Glutamate excitotoxicity is considered one of the major causes of retinal ganglion cell death in many retinal diseases. Retinal ganglion cell degeneration causes severe blindness since visual signals from the eye to the brain are conducted only through retinal ganglion cells. Objective: We aimed to explore the potential ameliorative effects of L. sativum against glutamate excitotoxicity-induced retinal ganglion cell damage. Methods: Pure retinal ganglion cells were divided into a control group (untreated); L. sativum -treated groups in which retinal ganglion cells were treated with 5, 10, 50, or 100 µg/mL L. sativum seed extract for 2 h; glutamate-treated groups in which cells were treated with 5, 10, 50, or 100 µM glutamate for 48 h; and L. sativum /glutamate groups [pretreatment with L. sativum for 2 h (50 or 100 µg/mL) before glutamate treatment at 100 µM for 48 h]. Cell damage was assessed by comet assay and cell viability was by MTT test. Results: Tailed DNA, tail length, and tail moment of the 50 and 100 mM glutamate-treated groups were significantly greater than those of the blank control group, while the L. sativum -treated groups demonstrated nonsignificantly different tailed DNA, tail length, and tail moment compared with the blank control group, but significantly lower values compared with the glutamate-treated groups. Conclusion: L. sativum ameliorated the cell viability in retinal ganglion cells after high-concentration glutamate exposure. L. sativum seed extracts were efficient anti-excitotoxic and antioxidant agent that might improve the clinical presentation of many neurological disorders.

Background Circular RNA (circRNA) plays an essential role in tumor progression, including glioma. circ_0030018 is a newly discovered circRNA that is highly expressed in glioma. However, its role and mechanism in glioma need to be further elucidated. Methods The expression of circ_0030018, microRNA (miR)-194-5p, and tripartite motif containing 44 (TRIM44) was examined using quantitative real-time PCR. Cell proliferation, migration, invasion, and apoptosis were determined using MTT assay, colony formation assay, transwell assay, and flow cytometry. Moreover, dual-luciferase reporter assay and RNA pull-down assay were used to verify the interactions among circ_0030018, miR-194-5p, and TRIM44 . The protein expression of TRIM44 was assessed by western blot analysis. Animal experiments were conducted to explore the role of circ_0030018 in glioma tumor growth in vivo . Results circ_0030018 was overexpressed in glioma tissues and cells, and its silencing could inhibit glioma cell proliferation, migration, invasion, and accelerate apoptosis. miR-194-5p could be sponged by circ_0030018, and its overexpression could hinder the progression of glioma cells. Further experiments revealed that miR-194-5p inhibitor reversed the negative regulation of circ_0030018 knockdown on glioma cell progression. In addition, TRIM44 was a target of miR-194-5p, and its downregulation could repress glioma cell progression. Overexpressed TRIM44 reversed the inhibition effect of miR-194-5p on glioma cell progression. Animal experiments suggested that circ_0030018 knockdown could reduce glioma tumor growth through regulating miR-194-5p and TRIM44. Conclusion Our 8data showed that circ_0030018 enhanced glioma progression by sponging miR-194-5p to regulate TRIM44, indicating that circ_0030018 might be a potential treatment target for glioma.

Nicotine withdrawal symptoms, mainly anxiety, cause high level of relapse rate after quitting smoking. Vitamin D supplementation has shown its potential for the prevention and treatment of anxiety disorders; however, neurobiological studies about the effect of vitamin D on nicotine withdrawal-induced anxiety are limited. To investigate the effect and molecular mechanism of vitamin D3 supplement by dietary on anxiety-like behavior during nicotine withdrawal, male C57/BL6 mice were divided into four groups: vehicle, nicotine only, vitamin D3 only, and nicotine plus vitamin D3. Mice were administrated with nicotine in drinking water (200 µg/mL), and vitamin D3 in feed for 6 weeks. During nicotine withdrawal, vitamin D3-treated mice showed significantly less anxiety-like behavior by an open-field test and marble buried test that performed an increase in the duration of the central zone and a decrease buried marble, respectively. Moreover, vitamin D3 supplementation attenuated the hippocampal NR2A expression on both protein and mRNA levels in nicotine and vitamin D3-treated mice. Our data showed that dietary supplementation with vitamin D3 ameliorated nicotine withdrawal-induced anxiety, which may be related to downregulation of NR2A expression in hippocampus. Vitamin D3 may provide a new dietary intervention with the easy access for smoking cessation.

During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies) during the wake–sleep cycle. Neural oscillations are electrobiomarkers of the connectivity state within systems. A single-systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method that is able to normalize ketamine-induced increase in gamma-frequency (30–80 Hz) oscillations and decrease in sigma-frequency (10–17 Hz) oscillations. Unilateral and bipolar frontoparietal (FP), transcranial anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant bilateral electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously occurring oscillations. A 5 min FP anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced gamma hyperactivity, and sigma hypoactivity at least in the bilateral parietal cortex. A duration effect was also recorded. The tDCS also tended to diminish the ketamine-induced delta hypoactivity. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.

Background and purpose Alzheimer’s disease (AD) is a neurodegeneration disease. The previous work from our research group demonstrated the neuroprotective effects of tripchlorolide (T4) in AD animal models. Materials and methods Neprilysin (NEP) is known as an important physiological amyloid-β protein (Aβ) peptide-degrading enzyme in the brain due to its apparent rate-limiting function. In this study, we explored the effect of NEP on AD model N2a/APP695 cells. Western blots and enzyme-linked immunosorbent assays were performed to assess the expression of proteins, while quantitative real-time polymerase chain reaction assays were used to evaluate RNA levels. Cell vitality was detected by the MTT assay, and reactive oxygen species (ROS) levels were assessed using a ROS activity assay kit. Results We discovered that T4 was able to enhance the enzyme activity of NEP. T4 administration decreased the protein levels of the soluble amyloid precursor protein. In further experiments, we found that by using thiorphan the secretion of Aβ, oxidative stress, nitrosative stress, and inflammatory factors, which were suppressed by T4, were reversed. Due to its ability to attenuate Aβ generation and to protect neurons against the neurotoxicity of Aβ, T4 may be a potential therapy in the regulation of Aβ-related pathology in AD by affecting NEP activity. Conclusion Tripchlorolide attenuates Aβ generation by inducing NEP activity in N2a/APP695 cells.

Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

Background The primary features of malignant glioma include high rates of mortality and recurrence, uncontrollable invasiveness, strong angiogenesis, and widespread hypoxia. The hypoxic microenvironment is an important factor affecting the malignant progression of glioma. However, the molecular mechanisms underlying glioma adaption in hypoxic microenvironments are poorly understood. Objective The work presented in this paper focuses on the role of WNK3 gene in glioma invasion under hypoxic conditions. Furthermore, we aim to explore its role in epithelial-to-mesenchymal transition (EMT). Methods ShRNA targeting WNK3 transfection was used to knockdown the WNK3 expression in U87 cells. We used western blot analysis to detect the relative expression of proteins in U87 cells. The effect of WNK3 on cell migration was explored using a transwell assay in the U87 cell line. We also evaluated WNK3 expression levels in glioma samples by immunohistochemistry analysis. Results WNK3 expression was significantly higher in high-grade (III and IV) gliomas than in low-grade (I and II) gliomas. WNK3 expression was up-regulated in U87 cells when cultured in a hypoxic environment in addition; WNK3 knockdown inhibited the invasion of U87 glioma cells by regulating the EMT, especially under hypoxic conditions. Conclusion These findings suggested that WNK3 plays an important role in the hypoxic microenvironment of glioma and might also be a candidate for therapeutic application in the treatment of glioma.

Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

Formaldehyde (FA) is a commercially important chemical applied in industry and scientific research. However, FA has a distinct impact on learning and memory. Although the mechanisms of FA toxicity have been well studied, additional research is required to establish the mechanisms of neuroprotection in cases of FA exposure. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid with a variety of health benefits, including the enhancement of learning and memory. In this study, we investigated the neuroprotective effects of DHA in Drosophila melanogaster that had ingested FA. Our data suggested that DHA enhanced reproductive processes, leading to an increase in the number of eggs, larvae, and adults. Surprisingly, we found that DHA had a mild protective effect against FA-induced impairments in learning and memory.

Background Training a non-dominant hand is important for rehabilitating people who are required to change handedness. However, improving the dexterity in using chopsticks with a non-dominant hand through training remains unclear. This study is aimed to measure whether chopstick training improves non-dominant hand chopstick operation skills and leads to acquisition of skill levels similar to those of the dominant hand. Methods This single-blinded randomized controlled trial enrolled 34 healthy young right-handed subjects who scored >70 points on the Edinburgh Handedness Questionnaire Inventory. They were randomly allocated to training or control groups. The training group participated in a 6-week chopstick training program with the non-dominant left hand, while the control group did not. Asymmetry of chopstick operation skill, perceived psychological stress, and oxygen-hemoglobin concentration as a brain activity measure in each hemisphere were measured before and after training. Results Participants in the training group had significantly lower asymmetry than those in the control group during the post-training assessment ( F [1,30] ≥ 5.54, p ≤ 0.03, partial η 2 ≥ 0.156). Only perceived psychological stress had a significantly higher asymmetry during the post-training assessment ( t [15] = 3.81, p < 0.01). Conclusion Six weeks of chopstick training improved non-dominant chopstick operation skills, and a performance level similar to that of the dominant hand was acquired.

Background Postpartum depression (PPD) is a frequent mental disorder after delivery. In China, most parturients give birth with the assistance of labor analgesia (LA) or by cesarean section (CS); however, it is still unclear whether these two approaches reveal different effects on PPD. Methods One hundred and ninety-eight patients with single pregnancy at full term were allocated to receive either group LA or group CS. Maternal and neonatal variables in the perinatal period were recorded. Multivariate logistical regression analysis was conducted to evaluate the associated factors of PPD. Results The incidence of PPD in group LA was lower than in group CS. Besides, eight factors were found to be potential predictors of PPD. Multivariate logistic model showed that LA was a protective factor against PPD. However, high family income and Edinburgh postnatal depression scale (EPDS) scores at 3 days postpartum were associated with an increased risk of PPD. Conclusion LA could reduce the incidence of PPD in women with single pregnancy at full term. Family income and EPDS scores in the early postpartum period were also related with PPD. Large sample size studies are needed to verify the impact of LA on the psychological states of postpartum women.

Epidemiological evidence has shown that smoking is associated with an increased risk of hearing loss. However, the underlying mechanisms regarding the impact of nicotine on the cochlea remain unclear. This study aimed to investigate the cytotoxic effects of nicotine on cochlear cells using cultured cochlear basilar membranes. Cochlear basilar membranes were isolated from newborn rats, cultured, and treated with 1–100 ng/mL nicotine for 48 h. Cuticular plates and stereocilia bundle staining were used to evaluate hair cell (HC) loss. Spiral ganglion neuron and acoustic nerve fiber staining were assessed to evaluate cochlear neural injury. Scanning electron microscopy and transmission electron microscopy imaging were employed to examine cochlear ultrastructural changes. Our results showed that compared to spiral ganglia and nerve fibers, HCs are more susceptible to nicotine-induced toxicity. HC loss was more severe in the basal turn than in the middle and apical turns, while nerve fibers and spiral ganglion cells were morphologically maintained. Ultrastructural changes revealed disordered and damaged stereocilia, swelling and decreased mitochondrial density, swelling, and degranulation of the endoplasmic reticulum. Our results suggest that nicotine causes HCs’ degeneration and loss and may have implications for smoking-related hearing loss.

Introduction Damage to the cerebellar functional network may underlie anxiety symptoms in patients with Parkinson’s disease (PD). Herein we investigated the regional homogeneity (ReHo) and functional connectivity (FC) patterns of cerebellar and clinical correlates in PD patients with anxiety and explored their clinical significance. Methods We enrolled 50 newly diagnosed drug-naïve PD patients and 30 normal controls (NCs). Twenty-six PD patients with anxiety symptoms (PD-A) and 24 PD patients without anxiety symptoms (PD-NA) were sorted into groups based on the Hamilton Anxiety Scale (HAMA). All included participants underwent rest-state functional magnetic resonance imaging (rs-fMRI) scanning. Cerebellar FC based on the seed-based method was used to investigate regional and whole brain function in PD-A, PD-NA, and NCs, and the relationship between the abnormal brain function and anxiety symptoms in PD patients was also detected. Results Compared with the PD-NA group and the NCs, the ReHo value of the PD-A group was significantly decreased in the left medial frontal gyrus and increased in the left cerebellum. Further, left-cerebellum-based FC patterns were used to detect the decreased FC in the right cerebellum, while FC was increased in the right caudate nucleus, and the right anterior cingulate cortex (ACC) in the PD-A group was compared with that in the PD-NA group. Further, the altered FC between the left cerebellum and the right cerebellum was significantly associated with anxiety symptoms in the PD-A group. Conclusion The present study found abnormal regional cerebellum function as well as disruptions in the connectivity network within the cerebellum, caudate, and ACC in patients with PD-A. In addition, the FC between the left cerebellum and the right cerebellum was associated with anxiety symptoms in patients with PD. The present study indicated that cerebellar functional damage may be associated with anxiety symptoms in PD patients.

Hypertension is one of the most reported cardiovascular and cerebrovascular diseases with significantly high morbidity and mortality rates. This condition threatens the very existence of human beings. Numerous studies conducted earlier revealed the good therapeutic effect of isorhynchophylline on hypertension since the former regulates the metabolic disorders in neurotransmitters. However, the mechanism behind this action is yet to be deciphered. The current study followed the targeted metabolomics method to investigate the changes in the neurotransmitter level in the hippocampus of spontaneously hypertensive rats (SHRs) after the rats were treated with isorhynchophylline. The authors predicted the metabolic pathways involved in extensively modified neurotransmitters. Further, the expressions of metabolism-key enzymes in mRNA and protein levels were also determined. When treated with isorhynchophylline, it induced notably varying metabolomic profiles of the hippocampus in SHRs. Isorhynchophylline perturbed a total of seven extensively modified neurotransmitters as well as the primarily related pathways such as tyrosine and glutamate metabolism. An increase in the key metabolic enzymes such as DDC, MAO, COMT, TH, and DβH was observed in the SHR group, whereas their levels decreased after treatment with isorhynchophylline. The expression of GAD67 established cross-current validity. So, isorhynchophylline has been proved to have potential therapeutic value to treat hypertension via tyrosine and glutamate metabolism in the hippocampus. Further, the current study also opened new ventures to further investigate the working mechanism of isorhynchophylline in hypertension.

The prefrontal dopamine D1 receptor (D1R) is involved in cognitive processes. Viral overexpression of this receptor in rats further increases the reward-related behaviors and even its termination induces anhedonia and helplessness. In this study, we investigated the risky decision-making during D1R overexpression and its termination. Rats conducted the rodent version of the Iowa gambling task daily. In addition, the methyl CpG–binding protein-2 (MeCP2), one regulator connecting the dopaminergic system, cognitive processes, and mood-related behavior, was investigated after completion of the behavioral tasks. D1R overexpressing subjects exhibited maladaptive risky decision-making and risky decisions returned to control levels following termination of D1R overexpression; however, after termination, animals earned less reward compared to control subjects. In this phase, MeCP2-positive cells were elevated in the right amygdala. Our results extend the previously reported behavioral changes in the D1R-manipulated animal model to increased risk-taking and revealed differential MeCP2 expression adding further evidence for a bipolar disorder-like phenotype of this model.

Background Diabetes mellitus (DM) has detrimental effects on the function of microvascular beds, resulting in blood–brain barrier (BBB) dysfunction. The objective of the study was to investigate whether DM affects the brain physiology through composition of cerebrospinal fluid (CSF) and compare gas tension and electrolyte levels in CSF between the diabetic and nondiabetic populations. Methods Patients aged between 20 and 70 years scheduled for elective orthopedic or urologic surgery requiring spinal anesthesia were enrolled. They were assigned to either of the two groups (control or type 2 DM). Gas tension and electrolytes in the CSF and whole blood samples were measured in both groups. Results All 49 enrolled patients (24 in the control and 25 in the DM group) completed the study. The concentrations of Na + and Mg 2+ in the blood were significantly lower in the DM group than those in the control. The levels of pCO 2 and HCO 3 − {\text{HCO}}_{3}^{-} in the CSF were lower in the DM group than in the control group. In addition, there was a marked increase in the glucose level in both the blood and CSF in the DM group. Conclusion The results show that there were some homeostatic changes in blood and CSF in patients with DM.

Circular RNAs contribute to the progression of glioma. However, the biological role and underlying mechanism of circ_0082375 in glioma remain unclear. Quantitative real-time PCR and Western blot assay were used to evaluate the expression levels of circ_0082375, microRNA-485-5p, and Wnt family member 7B (Wnt7B). The overall survival of glioma patients was estimated by the Kaplan–Meier curve. Cell proliferation, apoptosis, invasion, and migration were detected by cell counting kit-8, 5-ethynyl-2 -deoxyuridine (EdU) staining, flow cytometry, and transwell assays, respectively. Glucose level and lactate production were determined using glucose and lactate assay kits. In vitro angiogenesis assay was used to evaluate the angiogenesis of glioma cells. The interaction between microRNA (miR)-485-5p and circ_0082375 or Wnt family member 7B (Wnt7B) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft model was used to verify the function of circ_0082375 in vivo . circ_0082375 was upregulated in glioma tissues, and it was closely related to the prognosis of glioma patients. circ_0082375 knockdown suppressed cell proliferation, migration, invasion, angiogenesis, glycolysis, and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in glioma cells. irc_0082375 was a sponge of miR-485-5p, which directly targeted Wnt7B. Knockdown of circ_0082375 inhibited the malignancy, angiogenesis, and glycolysis of glioma cells in vitro by sponging miR-485-5p. Besides, circ_0082375 knockdown hampered the growth of glioma growth by regulating the miR-485-5p/Wnt7B axis in vivo. Altogether, circ_0082375 regulated miR-485-5p/Wnt7B axis to promote the malignancy, angiogenesis, and glycolysis of glioma cells, thereby contributing to the progression of glioma.

Objectives Cryptotanshinone (CPT), a natural quinoid diterpene, isolated from Salvia miltiorrhiza , has shown various pharmacological properties. However, its effect on chronic unpredictable stress (CUS)-induced depression phenotypes and the underlying mechanism remain unclear. Therefore, the aim of this study was to investigate whether CPT could exert an antidepressant effect. Methods We investigated the effects of CPT in a CUS-induced depression model and explored whether these effects were related to the anti-inflammatory and neurogenesis promoting properties by investigating the expression levels of various signaling molecules at the mRNA and protein levels. Results Administration of CPT improved depression-like behaviors in CUS-induced mice. CPT administration increased the levels of doublecortin-positive cells and reversed the decrease in the expression levels of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling transduction, as well as the downstream functional proteins, phosphorylated extracellular regulated protein kinases (p-ERK), and cyclic adenosine monophosphate (cAMP)-response element-binding protein levels (p-CREB) in hippocampus. CPT treatment also inhibited the activation of microglia and suppressed M1 microglial polarization, while promoting M2 microglial polarization by monitoring the expression levels of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), and further inhibited the expression of proinflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), and increased the expression of the anti-inflammatory cytokine IL-10 by regulating nuclear factor-κB (NF-κB) activation. Conclusions CPT relieves the depressive-like state in CUS-induced mice by enhancing neurogenesis and inhibiting inflammation through the BDNF/TrkB and NF-κB pathways and could therefore serve as a promising candidate for the treatment of depression.

A brain–computer interface (BCI) based on kinesthetic motor imagery has a potential of becoming a groundbreaking technology in a clinical setting. However, few studies focus on a visual-motor imagery (VMI) paradigm driving BCI. The VMI-BCI feature extraction methods are yet to be explored in depth. In this study, a novel VMI-BCI paradigm is proposed to execute four VMI tasks: imagining a car moving forward, reversing, turning left, and turning right. These mental strategies can naturally control a car or robot to move forward, backward, left, and right. Electroencephalogram (EEG) data from 25 subjects were collected. After the raw EEG signal baseline was corrected, the alpha band was extracted using bandpass filtering. The artifacts were removed by independent component analysis. Then, the EEG average instantaneous energy induced by VMI (VMI-EEG) was calculated using the Hilbert–Huang transform (HHT). The autoregressive model was extracted to construct a 12-dimensional feature vector to a support vector machine suitable for small sample classification. This was classified into two-class tasks: visual imagination of driving the car forward versus reversing, driving forward versus turning left, driving forward versus turning right, reversing versus turning left, reversing versus turning right, and turning left versus turning right. The results showed that the average classification accuracy of these two-class tasks was 62.68 ± 5.08%, and the highest classification accuracy was 73.66 ± 6.80%. The study showed that EEG features of O1 and O2 electrodes in the occipital region extracted by HHT were separable for these VMI tasks.

Background Dynamic balance is associated with fall risk. The aim of this study is to explore the effects of galvanic vestibular stimulation with very low intensity direct current (dcGVS) on dynamic balance. Methodology We used a rocker force platform for assessing the dynamic balance performance. Center-of-pressure (COP) coordinates were acquired and decomposed to rambling (RA) and trembling (TR). We measured sway parameters, including length, average speed, and average range, affected by dcGVS at 0.01 mA with eyes open (EO) and eyes closed (EC). Results We assessed 33 young healthy subjects and found that all sway parameters were shorter in the EO condition, indicating a better dynamic balance performance. dcGVS significantly improved the dynamic balance performance both in EO and EC conditions. All the sway parameters in COP in EO were significantly shorter than those in EC, indicating a better dynamic balance performance in EO. In EO, RA had greater improvement rates than TR. In EC, only average speed had a greater improvement rate in RA, whereas length and average range had greater improvement rates in TR. These results indicate a different modulation model between EO and EC. Conclusion These findings indicate that very low intensity dcGVS improved the sway parameters of dynamic balance in young healthy subjects. Moreover, our results suggest different dynamic balance control models between having EO and EC. The mechanisms of these phenomena caused by very low intensity dcGVS require further investigation.

Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.

Objective Alzheimer’s disease (AD) is a threatening disease for African populations in the upcoming years because of the increase in their expectancy of life. Here, we investigated whether natural products from Chrysophyllum perpulchrum as catechin and two dimeric procyanidins (catechin + hexose) could prevent progression of oxidative stress and cognitive changes using an AD-like rat model induced by Aβ 1-40 injection into the hippocampal CA1 subfield. Methodology Adult male Wistar rats were either microinjected with 1% ammonia as a vehicle (10 µL) or aggregated Aβ 1-40 at 10 µg bilateral hippocampus. On the 14th day of post-surgery, some Aβ rats were treated with melatonin (10 mg/kg i.p.) or with the Chrysophyllum perpulchrum extract (300 mg/kg p.o.), and some sham-operated rats received the extract alone. Cognitive abilities were tested with Y-maze, object recognition test and Morris Water Maze. Oxidative stress markers as well as the level of activated microglial cells were assayed in the brain. Results Aβ rats exhibited significant deficits of recognition memory and spatial learning. This was associated with an increase of microglia Iba 1 immunoreactivity as well as nitric oxide (NO), malondialdehyde and superoxide dismutase levels but not to the thiol content in the hippocampus, prefrontal cortex and septum of AD-like rats. The Chrysophyllum perpulchrum extract treatment mitigated Aβ-induced cognitive impairments and reversed microglia overactivation and subsequent generation of oxidative stress markers. Interestingly, the neuroprotective actions of the Chrysophyllum perpulchrum extract seem to be comparable to the control drug melatonin used albeit with some more beneficial effects. Conclusion These findings are preliminary and should be strengthened by more pharmacological studies of bioactive compounds of Chrysophyllum perpulchrum before being proposed as a promising drug against AD.

Objectives Hypoxic–ischemic brain damage (HIBD) is a major cause of brain injury in neonates. Bone marrow mesenchymal stem cells (BMSCs) show therapeutic potential for HIBD, and genetic modification may enhance their neuroprotective effects. The goal of this study was to investigate the neuroprotective effects of hepatocyte growth factor (HGF)-overexpressing BMSCs (BMSCs-HGF) against HIBD and their underlying mechanisms. Methods: BMSCs were transfected with HGF using adenoviral vectors. HIBD models were established and then BMSCs were transplanted into the brains of HIBD rats via intraventricular injection. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure cerebral infarction volumes. In vitro , primary cultured cortical neurons were co-cultured with BMSCs in a Transwell plate system. Oxygen–glucose deprivation (OGD) was applied to imitate hypoxic–ischemic insult, and PD98059 was added to the culture medium to block the phosphorylation of extracellular signal-regulated kinase (ERK). Cell apoptosis was determined using TUNEL staining. The expression of HGF was measured by immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blots. The expression of phosphorylated ERK (p-ERK) and B-cell lymphoma-2 (Bcl-2) was measured by western blots. Results HGF-gene transfection promoted BMSC proliferation. Moreover, BMSCs-HGF decreased HIBD-induced cerebral infarction volumes and enhanced the protective effects of the BMSCs against HIBD. BMSCs-HGF also increased expression of HGF, p-ERK, and Bcl-2 in brain tissues. In vitro , BMSC-HGF protected neurons against OGD-induced apoptosis. Inhibition of ERK phosphorylation abolished the neuroprotective effect of BMSCs-HGF against OGD. Conclusions BMSCs-HGF is a potential treatment for HIBD and that the ERK/Bcl-2 pathway is involved in the underlying neuroprotective mechanism.

It is proposed that gluten- and casein-rich diets (GRD and CRD) can synergistically exacerbate dysbiosis as comorbidity in autism by worsening leaky gut that affects the brain through the gut–brain axis. In this study, 35 young male rats were divided into 7 groups, Group 1 serves as control; Group 2, clindamycin (CL)-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism. These three groups were fed standard diet until the end of the experiment. Groups 4–7 are rats treated similarly with CL and PPA, then fed on CRD or GRD until the end of the experiment. Serum zonulin, glutathione (GSH), lipid peroxides, and gut microbial composition were measured in the seven studied groups. Data demonstrate the significant increase in serum zonulin as marker of leaky gut in the CL-treated groups fed on CRD or GRD. Lipid peroxides were significantly higher in the serum of GRD-fed rats compared to CRD-fed or normal diet-fed rats. GSH was much lower in CL-treated groups fed on CRD or GRD compared to PPA-treated rats fed on both diets. Both diets differentially affected the diversity of the gut microbiota. This study demonstrates that CRD and GRD exacerbates leaky gut, according to serum zonulin, which was used as marker for increased gut permeability.

Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep–wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep–wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz and 90 µA over 24 h to test the modulating effects of DBS on sleep–wake proportions, stability and spectral power in relation to the baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep (SWS) as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, as evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep–wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on the sleep–wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

Epilepsy is one of the most prevalent neurological disorders and can result in neuronal injury and degeneration. Consequently, research into new antiepileptic drugs capable of providing protection against neuronal injury and degeneration is extremely important. Neuronal Cx36 gap junction channels have been found to play an important role in epilepsy; thus, pharmacological interference using Cx36 gap junction channel blockers may be a promising strategy for disrupting the synchronization of neurons during seizure activity and protecting neurons. Based on these promising findings, several in vivo and in vitro studies are ongoing and the first encouraging results have been published. The results bring hope that neurons can be protected from injury and degeneration in patients with epilepsy, which is currently impossible.

Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders characterized by impairments activities without efficient pharmacological therapies in social interaction, speech and stereotypic patterns. Clinical studies have shown the efficacy of acupuncture as an alternative therapy for autism. The effectiveness of acupuncture as an alternative treatment for autism has been demonstrated through clinical trials. However, the molecular mechanisms that underlie these effects remain unclear. Due to its profound pro-social, anxiolytic, stress management effects, and its potential use for the treatment of psychiatric disorders associated with altered socioemotional competence, oxytocin (OT) released from the hypothalamus has attracted considerable interest. In the past decade, a number of clinical and animal studies have shown that OT administration effectively reduces core symptoms of ASD, especially social behavior deficits. Recently, the endocannabinoid system has emerged as a promising target for the treatment of autism. OT was found to facilitate the endocannabinoid-mediated social reward processes in the nucleus accumbens of the mouse brain. Furthermore, serotonin and dopamine are involved in the reward response mediated by OT. In view of these findings, we conclude that acupuncture may produce therapeutic effects on autism by triggering the hypothalamic oxytocin system, which in turn activates the release of neurotransmitters such as endocannabinoids, dopamine and serotonin. This would be a valuable guide for further research on the mechanism of treatment of autism with acupuncture.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several in vitro and in vivo experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

Major depressive disorder (MDD) is a common mental health disorder that brings severe disease burden worldwide. Traditional antidepressants are mainly targeted at monoamine neurotransmitters, with low remission rates and high recurrence rates. Ketamine is a noncompetitive glutamate N -methyl- d -aspartate receptor (NMDAR) antagonist, and its rapid and powerful antidepressant effects have come to light. Its antidepressant mechanism is still unclarified. Research found that ketamine had not only antagonistic effect on NMDAR but also strong immunomodulatory effect, both of which were closely related to the pathophysiology of MDD. Although there are many related studies, they are relatively heterogeneous. Therefore, this review mainly describes the immune mechanisms involved in MDD and how ketamine plays an antidepressant role by regulating peripheral and central immune system, including peripheral inflammatory cytokines, central microglia, and astrocytes. This review summarizes the related research, finds out the deficiencies of current research, and provides ideas for future research and the development of novel antidepressants.

A prerequisite for nerve-sparing pelvic surgery is a thorough understanding of the topographic anatomy of the fine and intricate pelvic nerve networks, and their connections to the central nervous system. Insights into the functions of pelvic nerves will help to interpret disease symptoms correctly and improve treatment. In this article, we review the anatomy and physiology of autonomic pelvic nerves, including their topography and putative functions. The aim is to achieve a better understanding of the mechanisms of pelvic pain and functional disorders, as well as improve their diagnosis and treatment. The information will also serve as a basis for counseling patients with chronic illnesses. A profound understanding of pelvic neuroanatomy will permit complex surgery in the pelvis without relevant nerve injury.

Acute spinal cord injury (SCI) is a devastating condition that results in tremendous physical and psychological harm and a series of socioeconomic problems. Although neurons in the spinal cord need neurotrophic factors for their survival and development to reestablish their connections with their original targets, endogenous neurotrophic factors are scarce and the sustainable delivery of exogeneous neurotrophic factors is challenging. The widely studied neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, and glial cell-derived neurotrophic factor have a relatively short cycle that is not sufficient enough for functionally significant neural regeneration after SCI. In the past decades, scholars have tried a variety of cellular and viral vehicles as well as tissue engineering scaffolds to safely and sustainably deliver those necessary neurotrophic factors to the injury site, and achieved satisfactory neural repair and functional recovery on many occasions. Here, we review the neurotrophic factors that have been used in trials to treat SCI, and vehicles that were commonly used for their sustained delivery. Graphical abstract

Vitamin D supplementation has been shown to improve outcomes for patients suffering from a variety of illnesses such as stroke and cancer. Vitamin D deficiencies have been associated with longer hospital stays, greater severity of symptoms, and death in some complex cases. Due to vitamin D’s burgeoning role in improving patient outcomes, a new sector of research is focusing on the lesser-known implications of vitamin D on health. Traumatic brain injury (TBI) affects approximately 69 million people worldwide per year. Here, we summarize the current scientific understanding of vitamin D dynamics with TBI to elucidate a potential way to lessen the cascade of secondary damage after an initial insult, with the goal of improving overall patient outcomes. Because vitamin D supplementation has been correlated with better outcomes in other pathologies involving immune and inflammatory molecules, it is important to study the potential effect of vitamin D deficiency (VDD) and supplementation on TBI outcomes. Research on vitamin D supplementation in TBI remains in the preliminary stages. There is still much to learn about vitamin D deficiency, dosage, variants of supplementary forms, mechanisms, and its role in TBI.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high morbidity, disability, and fatality rate, significantly increasing the global burden of public health. The failure in drug discovery over the past decades has stressed the urgency and importance of seeking new perspectives. Recently, gut microbiome (GM), with the ability to communicate with the brain bidirectionally through the microbiome–gut–brain axis, has attracted much attention in AD-related studies, owing to their strong associations with amyloids, systematic and focal inflammation, impairment of vascular homeostasis and gut barrier, mitochondrial dysfunction, etc., making the regulation of GM, specifically supplementation of probiotics a promising candidate for AD treatment. This article aims to review the leading-edge knowledge concerning potential roles of GM in AD pathogenesis and of probiotics in its treatment and prevention.

Increasing scientific evidence demonstrates that the gut microbiota influences normal physiological homeostasis and contributes to pathogenesis, ranging from obesity to neurodegenerative diseases, such as Alzheimer’s disease (AD). Gut microbiota can interact with the central nervous system (CNS) through the microbiota-gut-brain axis. The interaction is mediated by microbial secretions, metabolic interventions, and neural stimulation. Here, we review and summarize the regulatory pathways (immune, neural, neuroendocrine, or metabolic systems) in the microbiota-gut-brain axis in AD pathogenesis. Besides, we highlight the significant roles of the intestinal epithelial barrier and blood–brain barrier (BBB) in the microbiota-gut-brain axis. During the progression of AD, there is a gradual shift in the gut microbiota and host co-metabolic relationship, leading to gut dysbiosis, and the imbalance of microbial secretions and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs). These products may affect the CNS metabolic state and immune balance through the microbiota-gut-brain axis. Further, we summarize the potential microbiota-gut-brain axis-targeted therapy including carbohydrates, probiotics, dietary measures, and propose new strategies toward the development of anti-AD drugs. Taken together, the data in this review suggest that remodeling the gut microbiota may present a tractable strategy in the management and development of new therapeutics against AD and other neurodegenerative diseases.

A novel pulsatile-perfusion technology, dubbed Brain Ex , has been shown to restore microcirculation and cellular functions in the pig brain, 4 h postmortem. This technology has generated enthusiasm for its translational value for human neuroresuscitation. I offer a critical analysis of the study and its methodology, providing several reasons for skepticism. This includes: all phenomena were observed at different degrees of hypothermia; the physiological and biochemical milieu of the experimental preparation is radically different than the clinical setting of hypoxic-ischemic brain injury; and the study is confounded by uncontrolled traumatic brain injury and lifelong stress in all the animals.

We describe a Chinese family with severe autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) and psychiatric problems in whom whole-exome family trio sequencing identified a heterozygous mutation in the potassium channel subfamily T, member 1 ( KCNT1 ), a sodium-gated potassium channel gene, which was a novel missense mutation c.2153A>T (p. Asp718Val). The typical characteristics of the three patients in the family were refractory epilepsy, acquired cognitive impairment, and psychiatric problems, which include hallucinations and suicidal thoughts and behaviors. The age at onset was found to be earlier in son and daughter of the proband than that of the proband, as proven by the proband’s history of an epileptic seizure at the age of 16 years and her son’s and daughter’s history of seizures at the age of 8 years. Magnetic resonance imaging findings were negative for any abnormalities. Because of psychiatric symptoms, these three patients were administered risperidone at different times during their illness. The protestor’s son had tried fenofibrate treatment, but clinical remission was unclear. In summary, our findings broadened the mutation database in relation to KCNT1 and implicated the sodium-gated potassium channel complex in ADNFLE, more broadly, in the pathogenesis of focal epilepsies.

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases with ataxia as the main clinical manifestation. The phenotypes, gene mutations, and involved sites of different subtypes show a high degree of heterogeneity. The incidence of SCA varies greatly among different subtypes and the case of SCA40 is extremely rare. The aim of this study is to report a rare case of SCA40 and systematically review the incidence, gene mutation, and phenotype of SCAs, especially SCA40.

Background Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since the first cases were observed in Wuhan, China. Patients with COVID-19 develop multiple neurological symptoms, including headache, disturbed consciousness, and paresthesia, in addition to systemic and respiratory symptoms. Case presentation We presented a 57-year-old woman admitted to the emergency department – in December 2020 – with complaints of slurred speech, confusion, and left upper limb weakness after one week of positive nasopharyngeal swab sample SARS-CoV-2. Conclusions While the patient had previous comorbidities like hypertension and diabetes, she had no prior history of ischemic stroke or thrombosis, so we conclude that unilateral acute basal ganglia infarction may be a unique neurological manifestation after COVID-19 infection in an elderly patient with previous comorbidities.

Hand spasticity with a flexor pattern is a common problem affecting stroke patients and can result in pain, contractures, esthetic concerns, skin maceration, and overall loss of function. Poststroke (≥6 months) hemiparetic adult patients having a Modified Ashworth Scale (MAS) score of ≥1 for metacarpophalangeal flexion and thumb adduction spasticity were selected to receive an ultrasound-guided 20% ethyl alcohol block performed perineurally at the level of the deep branch of the ulnar nerve. Their MAS scores were evaluated pretreatment at 1 month and the change in MAS scores was assessed using Wilcoxon’s test. The threshold for statistical significance was set at p < 0.05. The mean MAS score for the flexor muscles of the 5 MCP joints and for thumb adduction was reduced from 3.3 ± 0.5 at pretreatment to 0.9 ± 0.5 at 1 month after the injection for the 10 patients. One month after the injection, the MAS scores were significantly reduced compared with those at pretreatment ( p < 0.001), without complications. These are encouraging results showing that ultrasound-guided alcohol blocks of the deep branch of the ulnar nerve are safe and can help chronic stroke patients with metacarpophalangeal flexion and thumb adduction spasticity at 1 month.

Background Glioblastoma multiforme (GBM) is the leading cause of death among adult brain cancer patients. Glutathione peroxidase 2 (GPX2), as a factor in oxidative stress, plays an important role in carcinogenesis. However, its role in GBM has not been well established. The study aimed to investigate the clinical significance of GPX2 with GBM prognosis. Methods Data of GBM and healthy individuals were retrospectively collected from oncomine, cancer cell line encyclopedia (CCLE), gene expression profiling interactive analysis (GEPIA), UALCAN, and Human Protein Atlas. GPX2 mRNA expression was first assessed across various cancer types in oncomine and cancer cell lines from CCLE. The mRNA expression of GPX2 was compared between normal and GBM tissues using GEPIA (normal = 207; GBM = 163) and UALCAN (normal = 5; GBM = 156). The GPX2 methylation was analyzed using data from UALCAN (normal = 2; GBM = 140). The prognostic value of GPX2 in GBM was explored in GEPIA and UALCAN using Kaplan–Meier method. STRING database was used to construct protein–protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Statistical significance was set as <0.05. Results The current study revealed no significant differences in GPX2 expression between normal and GBM from GEPIA data ( P > 0.05) and UALCAN ( P = 0.257). Patients with higher GPX2 intended to have a poorer prognosis ( P = 0.0089). The KEGG pathways found that chemokine-signaling pathway were the more preferred. Conclusions The findings demonstrated that GPX2 might be a potential diagnosis and prognostic indicator for GBM. Chemokine-signaling pathway may be involved in GPX2 function.