Volume 13, Issue 1

Rodents are averse to bodies of water, and this aversion has been exploited in experiments designed to study stress in mice. However, a few studies have elucidated the characteristics of murine water aversion. In this study, we investigated how mice behave in and around areas filled with water. Using variants of the open field test that contained pools of water at corners or sides of the field, we recorded the movements of mice throughout the field under various conditions. When the water was 8 mm deep, the mice explored the water pool regardless of whether an object was placed within it, but when the water was 20 mm deep, the mice were less willing to enter it. When the mice were placed on a dry area surrounded by 3 mm-deep water, they explored the water, but when they were surrounded by 8 mm-deep water, they stayed within the dry area. Our results indicate that mice exhibit exploratory behaviours around water, they can recognise water depths and avoid unacceptably deep water, and their willingness to enter water may be reduced by situational anxiety. Our experimental method could be used to investigate water-related anxiety-like behaviours in mice.

Calmodulin-like skin protein (CLSP) inhibits Alzheimer’s disease (AD)-related neurotoxicity. The activity of CLSP is reduced in AD. To restore the CLSP activity, we developed a hybrid peptide named CLSPCOL, consisting of CLSP(1–61) and the collagen-homologous region (COL) of adiponectin. It was previously shown that the CLSPCOL-mediated restoration of the reduced CLSP activity alleviated memory impairment and neuronal synaptic loss in APPswe/PS1dE9 double transgenic mice (APP/PS1 mice) at an advanced phase. Here, we examined whether CLSPCOL is effective against the memory impairment of the APP/PS1 mice at an early phase, and the memory impairment, caused by the temporal disturbance of the cholinergic neurotransmission, that mimics a part of AD-linked neuronal abnormality. The CLSPCOL-mediated restoration of the CLSP activity corrected the impairment in acquisition of fear-conditioned memory at an early-phase AD model. A single subcutaneous injection of CLSPCOL rescued the short-term working memory impairment, caused by subcutaneous injection of scopolamine. We have concluded that CLSPCOL is a promising disease-modifying therapeutic agent for not only the advanced phase but also the early-phase AD. It also serves as a symptomatic modifier of AD by potentiating the cholinergic neurotransmission.

Objectives The surgical technique of STA–MCA double bypass is used to improve blood flow supplied by the distal middle cerebral artery (MCA) to the cerebral territory. This retrospective study from a single center aimed to compare the outcomes following STA–MCA double bypass in 12 patients with recurrent ischemic stroke. Materials and methods We retrospectively analyzed the data from patients with internal carotid artery occlusion (ICAO) who had undergone STA–MCA double bypass in our center from January 2016 to December 2020. The surgical indications, evaluation of circle of Willis (CoW), changes in cerebral hemodynamic, surgical results, and follow-up results were analyzed. Results Post-operative perfusion-weighted imaging showed hemodynamic improvement in all 12 patients. Ten patients (83.33%) showed clinical improvement, and 2 patients (16.67%) had stable disease. No intracranial infections or acute ischemic events occurred. The post-operative National Institutes of Health Stroke Scale score and modified Barther scores were significantly improved after 180 days of follow-up. Twenty three (96%) anastomoses maintain patency of their bypass vessels, and none had recurrent cerebral infarction during a minimum of 36 months follow-up. Conclusion In this small study, in patients with recurrent ischemic stroke without other types of treatment, STA–MCA double bypass surgery was more effective in the subgroup of patients with ICAO and poor blood supply to the CoW and an area of cerebral hypoperfusion that exceeded the area supplied by the MCA.

Backgound Low-density lipoprotein (LDL) cholesterol can lead to the occurrence of atherosclerotic plaques, but patients with normal LDL still have atherosclerotic plaques in clinical practice. With the proposal of LDL subclass, this experiment investigated the relationship between the LDL content of different subclasses and the stability of carotid plaques. Methods Plaque stability was suggested by carotid ultrasound results. 37 patients with stable plaques were classified into one group and 41 patients with unstable plaques were classified into another group. The data of age, glycosylated hemoglobin (Ghb), and homocysteine (Hcy) were collected. The contents of LDL subclasses were measured by LIPOPRINT system. The data of total cholesterol (TC), LDL cholesterol, and triglyceride (TG) were collected. The plaque stability was assessed by carotid artery color Doppler ultrasound and the intima-media thickness (IMT) was measured. Results The levels of LDL-1 subclass 19.00 (13.00, 27.50) and LDL-2 subclass (21.62 ± 7.24) in the stable plaque group were higher than those in the unstable plaque group ( p < 0.05). The levels of LDL-3 subclass (12.24 ± 4.58), LDL-4 subclass 5.00 (2.00, 9.00), and sd-LDL 0 (0.00, 3.00) in the unstable plaque group were higher than those in the stable plaque group ( p < 0.05). LDL-1 subclass (adjusted OR = 0.923 and p < 0.05), and LDL-3 subclass (adjusted OR = 1.176 and p < 0.05) were independent risk factors for plaque stability. Conclusion Elevated LDL1 is associated with stable plaques whereas LDL3 was found associated with unstable plaques.

Background The most commonly used experimental model for preclinical studies on peripheral nerve regeneration is the sciatic nerve injury model. However, no experimental study has been conducted to evaluate acute injury modes at the same time. Objective We conducted sciatic nerve transverse injury, clamp injury, keep epineurium and axon cutting injury, and chemical damage injury in rats to evaluate the degree of damage of the four different injury modes and the degree of self-repair after injury. Methods The sciatic nerve transverse injury model, clamp injury model, keep epineurium injury model, and chemical damage injury model were constructed. Then, the sciatic nerve function was assessed using clinical evaluation methods and electrophysiological examinations, as well as immunofluorescence and axonal counting assessments of the reconstructed nerve pathways. Results The evaluations showed that the transverse group had the lowest muscle action potential, sciatic functional index, nociceptive threshold, mechanical threshold, rate of wet gastrocnemius muscle weight, area of muscle fiber, and numbers of myelinated nerve fibers. The chemical group had the highest, while the clamp group and the keep epineurium group had medium. Conclusion Transverse injury models have the most stable effect among all damage models; chemical injury models self-recover quickly and damage incompletely with poor stability of effect; and clamp injury models and keep epineurium injury models have no significant differences in many ways with medium stability.

Background Propofol, an intravenous sedative-hypnotic agent, is demonstrated to have antioxidant properties. The purpose of this study is to investigate the functional roles of propofol in neuroblastoma cells. Methods The proliferation and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2 H -tetrazol-3-ium bromide (MTT), EdU, and flow cytometry assays, respectively. The protein expression level was quantified by western blot assay. Inflammation and oxidative stress were determined by measuring the release of inflammatory factors, along with intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to assess the expression levels of HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), and miR-519a-3p in cells. The interaction relationship between HOTAIRM1 and miR-519a-3p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Results Treatment with MPP + has been observed to induce apoptosis, oxidative stress, and inflammation in neuroblastoma cells, which were abolished by propofol or silencing of HOTAIRM1. Importantly, the increase of HOTAIRM1 and the decrease of miR-519a-3p caused by MPP + were reversed by propofol in neuroblastoma cells. In addition, miR-519a-3p was a target of HOTAIRM1, and inhibition of miR-519a-3p abolished HOTAIRM1 silencing-induced effects on neuroblastoma cells. Moreover, functional experiments revealed that propofol might weaken MPP + -induced apoptosis, oxidative stress, and inflammation by regulating the HOTAIRM1/miR-519a-3p axis. Conclusion Propofol inhibited oxidative stress and inflammation in MPP + -induced neuroblastoma cells by targeting the HOTAIRM1/miR-519a-3p axis, implying the potential protective function of propofol against oxidative damage.

Background The classical renin-angiotensin system (RAS) has an important role in the cardiovascular system and water homeostasis in the body. Recently, the existence of RAS with all of its components has been shown in the mammalian brain. RAS participates in many brain activities, including memory acquisition and consolidation. Since the cholinergic neurotransmission in the hippocampus is crucial for these functions, this study aims to evaluate the hippocampal angiotensin receptors (ATs) and choline acetyltransferase (ChAT) mRNA in the renovascular hypertensive rats in captopril- and losartan-treated hypertensive rats. Methods The rats were randomly divided into four groups of eight animals; sham, Goldblatt two kidney one clip (2K1C) hypertensive rats and Goldblatt 2K1C hypertensive rats received 5 mg/kg captopril and Goldblatt 2K1C hypertensive rats received 10 mg/kg losartan. After 8 days of treatment, the rats were sacrificed and angiotensin-converting enzyme (ACE), ChAT, AT1, and AT2 receptor mRNAs in the hippocampus of rats were assessed by real-time PCR. The Morris water maze test was applied to measure the cognitive functioning of the rats. Results Hypertensive rats showed impaired acquisition and memory function in the Morris water maze test. Treatment with ACE inhibitor (captopril) and AT1 receptor antagonist (losartan) reversed the observed acquisition and memory deficit in hypertensive rats. Overexpression of AChE, AT1, and AT2 and low expression of ChAT were noted in the hippocampus of rats with Goldblatt hypertension compared with that of the sham group. Treatment with captopril significantly reversed these changes, while treatment with losartan slightly reduced the mentioned effects. Conclusion The memory-enhancing effect of captopril in renovascular hypertensive rats might lead to increased hippocampal ChAT expression.

Fragile X syndrome (FXS) is a monogenic disorder characterized by intellectual disability and behavioral challenges. It is caused by aberrant methylation of the fragile X mental retardation 1 (FMR1) gene. Given the failure of clinical trials in FXS and growing evidence of a role of metabotropic glutamate subtype 5 receptors (mGluR5) in the pathophysiology of the disorder, we investigated mGluR5 function in FMR1 Knockout (FMR1-KO) mice and age- and sex-matched control mice using longitudinal positron emission tomography (PET) imaging to better understand the disorder. The studies were repeated at four time points to examine age- and disease-induced changes in mGluR5 availability using 3-fluoro-[ 18 F]5-(2-pyridinylethynyl)benzonitrile ([ 18 F]FPEB). We found that the binding potential (BP) of [ 18 F]FPEB was significantly lower in the KO mice in mGluR5-implicated brain areas including striatum, cortex, hippocampus, thalamus, and olfactory bulb. The BP also changed with age, regardless of disorder status, increasing in early adulthood in male but not in female mice before decreasing later in both sexes. The difference in mGluR5 availability between the FMR1-KO and control mice and the change in BP in the KO mice as a function of age and sex illustrate the nature of the disorder and its progression, providing mechanistic insights for treatment design.

Alzheimer’s disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E ( ApoE ) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE . Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE–TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.

Objective Several lines of evidence demonstrated the role of anesthetic drugs in cognitive functions. Some anesthetic agents have been confirmed to be associated with long-term spatial memory and learning in aged animal models. Methods C57BL/6 mice were divided into four different groups based on different concentrations of remimazolam treatments. Behavioral phenotype was observed by open field, rota rod, Morris water maze, and elevated plus maze test. Western blot was performed to see the expression pattern of different proteins. Confocal microscopy images were taken for neuronal and glial cells to see the effect of remimazolam on CNS cells. Results We showed that remimazolam, a new anesthetic drug, impaired cognitive behavior. Repetitive doses of remimazolam have been found to induce neuronal loss with a significant change in morphology. Here, we showed that a higher concentration of remimazolam had a significant effect on CNS cell activation. We showed that remimazolam caused memory dysfunction by inducing neuronal apoptosis via glutamate excitotoxicity. It also exhibited amyloid β plaque in the brain via abnormal phosphorylation of tau protein. Remimazolam-mediated regulation of glial cells in mouse cortex was observed and robust activation of astrocytes and microglial cells was found. Finally, we assessed the behavioral phenotype of mice and found that treatment with remimazolam induced significant behavioral changes and memory dysfunction. Conclusions This study provides insight into the mechanism of anesthetic drug-induced memory deficits and may help improve the therapeutic effects of anesthesia agents in clinical applications. Graphical abstract

Glial fibrillary acidic protein astrocytopathy (GFAP-A) is a rare autoimmune disease of the central nervous system that was newly reported in 2016. Previous studies have speculated that the pathological mechanism and clinical outcome of GFAP-A lie in the demyelination of the central nervous system, but due to the limitations of MR, this conclusion has not been further confirmed from the perspective of neuroimaging. A non-invasive, quantitative measurement of demyelination would be clinically valuable, given its critical role in mediating GFAP-A. Here, we report a case in which we use 18 F-florbetapir positron emission tomography-magnetic resonance imaging (PET/MRI) to evaluate myelin recovery with follow-up in the patient with GFAP-A. Our patient displayed a decreased uptake of PET tracer 18 F-florbetapir in the brain lesions and lower distribution volume ratio in the damaged white matter lesions compared to the normal-appearing white matter, indicating significant intracranial demyelination. After treatment, the 18 F-florbetapir PET/MRI examination showed a significant increase in the uptake of 18 F-florbetapir in the brain lesions, along with a reduced Expanded Disability Status Scale score. Although only a small number of patients have been validated, this case first reported 18 F-florbetapir PET/MRI could quantitatively and non-invasively assess the myelin recovery in GFAP-A patients, which may lead to improvements in the early diagnosis and long-term prognosis.

Background The first Chinese family with paroxysmal non-kinesigenic dystonia (PNKD) was confirmed to harbour a PNKD mutation. However, the pathogenic mechanism of the PNKD-causing gene mutation was unclear. Methods Wild-type and mutant PNKD-L plasmids were prepared and transfected into the C6 cell line to study the distribution and stability of PNKD protein in C6 cells and its effect on the glutathione content. The blood and cerebrospinal fluid (CSF) of 3 PNKD patients and 3 healthy controls were collected. The differentially expressed proteins were identified using isobaric tags for relative and absolute quantitation. Furthermore, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed, and the protein–protein interaction network was constructed. Results Wild-type PNKD protein was mainly distributed in the membranes, whereas mutant PNKD protein was distributed throughout the C6 cells. After transfection with mutant PNKD-L plasmid, the glutathione content decreased significantly in C6 cells; the stability of the mutant PNKD protein was significantly low. There were 172 and 163 differentially expressed proteins in CSF and plasma, respectively, of PNKD patients and healthy controls. For these proteins, blood microparticle and complex activation (classical pathway) were the common GO enrichment term, and complex and coordination cascade pathway were the common KEGG enrichment pathway. Recombinant mothers against decapentaplegic homolog 4 (SMAD4) was one of the differentially expressed proteins; it exhibited a relationship with the aforementioned enrichment GO terms and KEGG pathway. Conclusion PNKD protein was mainly distributed in cell membranes. PNKD-L mutation affected subcellular localisation, PNKD protein stability, and glutathione content. SMAD4 was found to be a potential biomarker for PNKD diagnosis.

Spatial learning and memory are used by all individuals who need to move in a space. Morris water maze (MWM) is an accepted method for its evaluation in murine models and has many protocols, ranging from the classic parameters of latency, distance, and number of crossings to the platform zone, to other more complex methods involving computerized trajectory analysis. Algorithm-based SS analysis is an alternative that enriches traditional classic parameters. We developed a non-computerized parameter-based Search Strategy Algorithm (SSA), to classify strategies and detect changes in spatial memory and learning. For this, our algorithm was validated using young and aged rats, evaluated by two observers who classified the trajectories of the rats based on the effectiveness, localization, and precision to reach the platform. SSA is classified into 10 categories, classified by effectiveness, initial direction, and precision. Traditional measurements were unable to show significant differences in the learning process. However, significant differences were identified in SSA. Young rats used a direct search strategy (SS), while aged rats preferred indirect ones. The number of platform crossings was the only variable to show the difference in the intermediate probe trial. The parameter-based algorithm represents an alternative to the computerized SS methods to analyze the spatial memory and learning process in young and age rats. We validate the use of SSA as an alternative to computerized SS analysis spatial learning acquisition. We demonstrated that aged rats had the ability to learn spatial memory tasks using different search strategies. The use of SSA resulted in a reliable and reproducible method to analyze MWM protocols.

Parkinson’s disease (PD), a progressive neurodegenerative disorder, affects dopaminergic neurons. Oxidative stress and gut damage play critical roles in PD pathogenesis. Inhibition of oxidative stress and gut damage can prevent neuronal death and delay PD progression. The objective of this study was to evaluate the therapeutic effect of embelin or the combination with levodopa (LD) in a rotenone-induced PD mouse model. At the end of experimentation, the mice were sacrificed and the midbrain was used to evaluate various biochemical parameters, such as nitric oxide, peroxynitrite, urea, and lipid peroxidation. In the substantia nigra (midbrain), tyrosine hydroxylase (TH) expression was examined by immunohistochemistry, and Nurr1 expression was evaluated by western blotting. Gut histopathology was evaluated on tissue sections stained with hematoxylin and eosin. In silico molecular docking studies of embelin and α-synuclein (α-syn) fibrils were also performed. Embelin alone or in combination with LD ameliorated oxidative stress and gut damage. TH and Nurr1 protein levels were also significantly restored. Docking studies confirmed the affinity of embelin toward α-syn. Taken together, embelin could be a promising drug for the treatment of PD, especially when combined with LD.

Background Inflammatory response is one of the important factors affecting the formation of intracranial aneurysm. miR-1246 is involved in the regulation of several inflammatory diseases; however, its expression levels and the mechanism of action in intracranial aneurysms remain further investigated. Methods Bioinformatics was used to analyze the levels of micro-RNAs (miRNAs) in the serum of intracranial aneurysm patients as well as in the intracranial aneurysm tissues downloaded from the GEO RNA-seq database. Blood samples were collected pre-operatively from patients with intracranial aneurysms as well as from healthy volunteers, and miRNA-1246 expression levels were detected using quantitative reverse transcriptase polymerase chain reaction. Meanwhile, the diagnostic value of miR-1246 for intracranial aneurysm was explored using the receiver operating characteristic (ROC) curve. Principle findings and results Serum levels of miR-1246 were elevated in intracranial aneurysm patients. Bioinformatics studies revealed that the target genes of miR-1246, TP53, glycogen synthetase kinase (GSK), and transcription factor YY1 may play important roles in the development of intracranial aneurysms. miR-1246 is involved in inflammatory response, lipid, and atherosclerotic signaling pathways. Conclusions and significance High level of miR-1246 is found in the serum of patients with intracranial aneurysms and may serve as a diagnostic or/and treatment marker for intracranial aneurysms.

Objective The aim of this study is to determine the factors that affect patients’ ability to carry out high dose of massed practice. Methods Patients with stroke were included in the study if they had no severe impairment in motor and cognitive functions. Dose of massed practice, motor function, perceived amount and quality of use of the arm in the real world, wrist and elbow flexors spasticity, dominant hand stroke, presence of shoulder pain, and central post-stroke pain were assessed on the first day. Dose of massed practice was assessed again on the second day. The data were analyzed using descriptive statistics and linear multiple regression. Results Only motor function ( β = –0.310, r = 0.787, P < 0.001), perceived amount of use ( β = 0.300, r = 0.823; 95% CI = 0.34–107.224, P = 0.049), severity of shoulder pain ( β = –0.155, r = –0.472, P = 0.019), wrist flexors spasticity ( β = –0.154, r = –0.421, P = 0.002), age ( β = –0.129, r = –0.366, P = 0.018), dominant hand stroke ( β = –0.091, r = –0.075, P = 0.041), and sex ( β = –0.090, r = –0.161, P = 0.036) significantly influenced patients’ ability to carry out high dose of massed practice. Conclusion Many factors affect patients’ ability to carry out high dose of massed practice. Understanding these factors can help in designing appropriate rehabilitation.

Introduction Transcranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude. Methods We investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1–1.4 s in a group of healthy subjects. Results We found no differences in TEP amplitude or GMFA between the first, second and last third of trials. Discussion Short IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity.

Background A specific biological vulnerability underlies suicidal behavior. Recent findings have suggested a possible role of inflammation and neuroaxonal injury. However, the relationship between inflammation and clinical symptoms in this disorder is still unclear. The objective of this study is applying novel blood markers of neuroaxonal integrity such as neurofilament light chain (NfL) and comparing the results with the healthy control subjects. Methods In this cross-sectional study patients with suicide attempts were evaluated. The serum concentration of NfL on admission was measured by enzyme-linked immunosorbent assays. Results A total of 50 patients with a suicide attempts and 35 healthy controls were included in the study. The levels of NfL in attempted suicide patients were significantly higher in comparison with healthy controls (40.52 ± 33.54 vs 13.73 ± 5.11, P < 0.001). A significant association between serum levels of NfL and risk factors for suicide was not found. Conclusion These findings indicate that axonal damage may be an underlying neuropathological component of suicide attempt patients, although no correlation was observed with clinical features. This line of work could lead to new horizons in understanding the neurobiology of suicidal attempts and the development of better management strategies for these patients.

Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 ± 2.7 vs 15.7 ± 2.0 mm 3 at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 ± 0.23 vs 1.00 ± 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 ± 3.1 vs 25.1 ± 4.7 cells/0.1 mm 2 ). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.

Exposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b , Emx2os , Bivm , Gm1439 , Prdm15 , and Rai2 . Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.

This study aimed to evaluate the protective and therapeutic potency of bee pollen and probiotic mixture on brain intoxication caused by propionic acid (PPA) in juvenile rats. Five groups of six animals each, were used: the control group only receiving phosphate-buffered saline; the bee pollen and probiotic-treated group receiving a combination of an equal quantity of bee pollen and probiotic (0.2 kg/kg body weight); the PPA group being treated for 3 days with an oral neurotoxic dose of PPA (0.25 kg/kg body weight); the protective and therapeutic groups receiving bee pollen and probiotic mixture treatment right before and after the neurotoxic dose of PPA, respectively. The levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α, and interferon γ (IFN-γ) were investigated to evaluate the neuroinflammatory responses in brain tissues from different animal groups. The much higher IL-1β, IL-8, and IFN-γ, as pro-inflammatory cytokines ( P < 0.001), together with much lower IL-10, as anti-inflammatory cytokine ( P < 0.001) compared to controls clearly demonstrated the neurotoxic effects of PPA. Interestingly, the mixture of bee pollen and probiotics was effective in alleviating PPA neurotoxic effects in both therapeutic and protective groups demonstrating highly significant changes in IL-1β, IL-8, IL-10, and IFN-γ levels together with non-significant reduction in IL-6 levels compared to PPA-treated rats. Overall, our findings demonstrated a new approach to the beneficial use of psychobiotics presenting as bee pollen and probiotic combination in neuroinflammation through cytokine changes as a possible role of glial cells in gut–brain axis.

Parkinson’s disease (PD) is a common neurodegenerative disease that severely affects the quality of life of patients. There is no specific drug for PD up to now. Previous studies have shown that neuroinflammation plays an important role in the pathogenesis of PD. Isoliquiritigenin (ILG) is thought to have a variety of biological activities including anti-inflammatory. However, to date, no studies have reported the role of ILG on neuroinflammation in PD in vivo . This study aimed to investigate the effect of ILG on PD in vivo and its mechanism, and to provide an experimental basis for clinical treatment of PD. Our results showed that ILG at a concentration of 20 mg/kg was effective in reducing the number of rotations in PD mice. In addition, ILG increased the expression of tyrosine hydroxylase and decreased the expression of α-synuclein. The results also showed that ILG reduced the expression of Iba1, IL-1β, IL-6, and TNF-α. Not only that, ILG also upregulated the expression of Nrf2 and NQO-1 in vivo . Our results suggest that ILG significantly attenuates neurological deficits in PD, and the mechanism may be through the activation of the Nrf2/NQO-1 signaling pathway to reduce neuroinflammation. Moreover, our findings provide a new therapeutic strategy for PD.

Background A growing number of studies have demonstrated that ketamine induces rapid and sustained antidepressant action. Neuronal nitric oxide synthase (nNOS) signaling has been explored for the treatment of neuropsychiatric disorders for decades. But the effect of ketamine on nNOS signaling is poorly understood. The aim of the present study was to investigate the effect of ketamine on nNOS signaling in a chronic unpredictable mild stress (CUMS) model of depression. Methods Forty-eight rats were randomly divided into four groups: the control group of healthy rats (group C), the healthy rats treated with ketamine 10 mg/kg for 3 days (group CK), the rats model of stress-induced depression group (group D), and the depressed group treated with ketamine 10 mg/kg for 3 days (group DK). The sucrose preference test and open field test were used to assess behavioral changes. Immunohistochemistry, immunofluorescence, and real-time PCR analysis were carried out to measure the expression of nNOS, CAPON, and Dexras1 in the prefrontal cortex (PFC) of the CUMS rats. Results Compared with healthy rats, the total distance traveled, the rearing counts, the sucrose preference percentage (SPP), and CAPON and Dexras1 expression in the PFC significantly decreased, while nNOS expression increased in CUMS rats. After treating with ketamine, the total distance traveled, the rearing counts, the SPP, and CAPON and Dexras1 expression significantly increased, while nNOS expression significantly decreased. Conclusion The results indicated that ketamine improved the depressive behavior of rats, which may be related to the reduced nNOS expression and enhanced CAPON and Dexras1 expression.

Background The CACNA1C protein is a L -type calcium channel, which influence affective disorders. Purpose The purpose of the present study was to examine the possible association between the different genotypes of rs100677 CACNA1C gene and anxiety and other clinical symptoms in patients with unipolar depression. Patients and controls A total of 754 patients and 708 controls from the Danish Psychiatric Biobank participated. Results A significant correlation was found between anxiety and the A allele. It was further found that patients with the A allele more often were treated with electroconvulsive therapy and patients with the AA phenotype had the highest age. Limitations The only information about controls was their sex and that they were recruited from the blood bank. Two types of inclusion criteria were used. The clinical data were not complete for all patients.

A kidney transplant is often the treatment of choice for end-stage kidney disease, compared with a lifetime on dialysis. Kidney transplant recipients (KTRs) have a reduced risk for new strokes than patients with chronic kidney disease (CKD) G5 treated by dialysis (CKD G5D). However, the benefit of Kidney transplant on post-stroke hospitalization outcomes has not been well studied. This study aimed to evaluate the outcomes of hospitalization after acute ischemic stroke (AIS) in KTRs and patients with CKD G5D. This retrospective study used patient data from the US Nationwide Inpatient Sample database. From 2005 to 2018, patients hospitalized with AIS were classified into 3 groups, including KTRs ( n = 1,833), patients with CKD G5D ( n = 26,767), and those without CKD (CKD-free, n = 986,945). Patients with CKD G1–G4 or unspecified stage, and graft failure requiring dialysis were excluded. In-hospital mortality, medical complications, transfer to nursing homes, and length of stay (LOS) were compared. Compared to CKD-free group, KTRs had no significant higher risks for in-hospital mortality, transfer to nursing homes, and LOS, but a greater risk for medical complications after adjusting for relevant factors. CKD G5D group had higher risks for in-hospital mortality (adjusted odds ratio (aOR): 2.04, 95% confidence interval (CI): 1.93–2.15), medical complications (aOR: 1.49, 95% CI: 1.45–1.54), and transfer to nursing homes (aOR: 1.10, 95% CI: 1.07–1.13), and a 0.07 day (95% CI: 0.06–0.08) longer LOS than CKD-free group. In conclusion, the outcomes of AIS hospitalization were more favorable in KTRs as compared with CKD G5D. Furthermore, the risks for in-hospital mortality, transfer to long-term care facilities, and LOS were not significantly different between KTRs and CKD-free patients.

We evaluated the accuracy of the quantitative and semiquantitative analysis in detecting regional atrophy patterns and differentiating mild cognitive impairment patients who remain stable (aMCI-S) from patients who develop Alzheimer’s disease (aMCI-AD) at clinical follow-up. Baseline magnetic resonance imaging was used for quantitative and semiquantitative analysis using visual rating scales. Visual rating scores were related to gray matter thicknesses or volume measures of some structures belonging to the same brain regions. Receiver operating characteristic (ROC) analysis was performed to assess measures’ accuracy in differentiating aMCI-S from aMCI-AD. Comparing aMCI-S and aMCI-AD patients, significant differences were found for specific rating scales, for cortical thickness belonging to the middle temporal lobe (MTL), anterior temporal (AT), and fronto-insular (FI) regions, for gray matter volumes belonging to MTL and AT regions. ROC curve analysis showed that middle temporal atrophy, AT, and FI visual scales showed better diagnostic accuracy than quantitative measures also when thickness measures were combined with hippocampal volumes. Semiquantitative evaluation, performed by trained observers, is a fast and reliable tool in differentiating, at the early stage of disease, aMCI patients that remain stable from those patients that may progress to AD since visual rating scales may be informative both about early hippocampal volume loss and cortical thickness reduction.

Objectives This study aimed to investigate the changes in serum levels of retinol-binding protein 4 (RBP4) with cerebral infarction, relationship of RBP4 with oxidative stress and carotid atherosclerosis, and its possible role in cerebral infarction. Materials and methods According to the results of cervical vascular ultrasound, the experimental group was divided into three groups: intima thickening group ( n = 31), stable plaque group ( n = 51), and unstable plaque group ( n = 54). Forty healthy subjects were selected as the control group. Their serum levels of RBP4, 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), and catalase (CAT) were measured. Carotid vascular ultrasound was used to measure the plaque area and intima-media thickness (IMT). Results The serum RBP4 and 8-iso-PGF2α levels, IMT and plaque area in the control, intimal thickening, stable plaque, and unstable plaque groups increased, while the serum level of CAT decreased ( P < 0.001). The serum levels of RBP4 positively correlated with 8-iso-PGF2α, IMT, and plaque area and negatively correlated with CAT level. The area under the receiver operating characteristic curve was 0.778 in predicting unstable plaques. Conclusions The serum levels of RBP4 were significantly elevated in elderly patients with cerebral infarction and correlated with oxidative stress injury and the degree of atherosclerosis. Serum RBP4 has diagnostic value for unstable plaques in carotid arteries.

Introduction Esophageal achalasia is a primary motility disorder. Although the exact pathogenesis is unknown, autoimmune, and neurodegenerative processes seem to be involved similarly to neurodegenerative and/or demyelinating disorders (NDDs). We hypothesized that the prevalence of NDD may be higher among patients with achalasia and vice versa as the background pathogenetic mechanisms are similar. Methods This was a prospective, comparative questionnaire-based study. Patients with achalasia and patients with NDD were enrolled. Selected patients with achalasia were thoroughly examined by a neurologist and selected patients with NDD were examined by a gastroenterologist to confirm or rule out NDD or achalasia. We assessed the prevalence of both achalasia and NDD and compared them with their prevalence in general population. Results A total of 150 patients with achalasia and 112 patients with NDD were enrolled. We observed an increased prevalence of NDD among patients with achalasia (6.0% (9/150); 95% CI (confidence interval): 3.1–11.2%) as compared to the estimated 2.0% prevalence in general population ( p = 0.003). Although 32 out of 112 patients (28.6%) with NDD reported dysphagia, we did not observe significantly increased prevalence of achalasia in these patients (1.8% (2/112) vs 0.8% in general population, p = 0.226). Conclusion The prevalence of NDD was significantly higher among patients with achalasia (6.0%) compared to general population (2.0%), suggesting an association of these disorders. Large-volume studies are necessary to confirm this finding.

Oxidative stress is considered as an important mechanism underlying the pathology of neurodegenerative disorders. In this study, we utilized an in vitro model where oxidative stress process was evoked by exogenous hydrogen peroxide (H 2 O 2 ) in HT22 murine hippocampal neurons and evaluated the neuroprotective effects of geissoschizine methyl ether (GME), a naturally occurring alkaloid from the hooks of Uncaria rhynchophylla (Miq.) Jacks. After a 24 h H 2 O 2 (350 μM) insult, a significant decrease in cell survival and a sharp increase in intracellular reactive oxygen species were observed in HT22 cells. Encouragingly, GME (10–200 μM) effectively reversed these abnormal cellular changes induced by H 2 O 2 . Moreover, mechanistic studies using Western blot revealed that GME inhibited the increase of phospho-ERK protein expression, but not phospho-p38, caused by H 2 O 2 . Molecular docking simulation further revealed a possible binding mode that GME inhibited ERK protein, showing that GME favorably bound to ERK via multiple hydrophobic and hydrogen bond interactions. These findings indicate that GME provide effective neuroprotection via inhibiting ERK pathway and also encourage further ex vivo and in vivo pharmacological investigations of GME in treating oxidative stress-mediated neurological disorders. Graphical abstract

N -Methyl- d -aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.

Background Acacetin (5,7-dihydroxy-4′-methoxyflavone), one of the main extractions from Saussurea involucrata , has anti-inflammatory effects. Our previous study found that acacetin inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) signaling pathway after cerebral ischemia–reperfusion injury. NLRP3 inflammasome plays a role in Alzheimer’s disease (AD) process. However, few studies have examined the effects of acacetin in AD. Methods We randomly divided APP swe/PS1dE9 double transgenic mice into acacetin group (intraperitoneal injection of 25 mg/kg acacetin) and AD model group (intraperitoneal injection of same volume of saline). C57BL/6 mice were selected as control group (same treatment with AD model group). After treating for 30 days, a Morris water maze test was conducted to evaluate spatial learning and memory of the mice. Senile plaque (SP) formation was evaluated by immunohistochemistry. NLRP3 inflammasome-related inflammatory factors and amyloid-β-42 were detected by Western blot or enzyme-linked immunosorbent assay. Results Acacetin improved spatial learning and memory of AD mice and reduced APP/β expression, thereby decreasing SP formation in the brain. Acacetin also reduced the expression of NLRP3, cysteinyl aspartate-specific proteinase 1 (caspase-1), and interleukin-1β (IL-1β) and the release of inflammatory factors, tumor necrosis factor-α (TNF-α) and IL-1β. Conclusions Acacetin improved the learning and memory abilities of AD mice and exerted a protective effect on AD by inhibiting the NLRP3 signaling pathway and reducing SP formation.

Background a purpose The collateral capacity of the circle of Willis (CoW) may play an important role in the development of ischemic strokes. The occurrence of classical polygon shows wide geographical variations and morphological data on diameters of the Willisian collaterals are scarce. We aimed to assess CoW variations and vessel diameters in a Central European cohort. Subjects and methods CoWs were removed during routine autopsy. The morphological pattern of the circles was recorded. The prepared circles were then put between two glass plates and tightly compressed. The length of the vessels and half of the circumference were measured under a light microscope enabling measurement with an approximation of 0.1 mm. Vessel diameters were calculated from vessel circumference. Results A total of 110 circles were analysed. Incomplete circles (missing one or two segments of CoW) were found in 25 cases (22.7%). Any forms of anatomical variations were detected in 14 cases (12.7%). When applying the <1 mm diameter threshold for analysis, 36 anterior communicating arteries (32.7%), 53 right posterior communicating arteries (48.2%), 73 left posterior communicating arteries (66.4%) and 18 posterior communicating arteries (16.3%) on both the sides were considered hypoplastic. Conclusions In patients without stroke in their history, complete CoW may be present in >60% of the cases. Our diameter data may serve as reference values for the Central-European population.

Brain metabolic-sensory targets for modulatory glucose-sensitive endocrine and neurochemical signals remain unidentified. A hypothalamic astrocyte primary culture model was here used to investigate whether glucocorticoid receptor (GR) and noradrenergic signals regulate astrocyte glucose (glucose transporter-2 [GLUT2], glucokinase) and/or energy (5′-AMP-activated protein kinase [AMPK]) sensor reactivity to glucoprivation by sex. Glucose-supplied astrocytes of each sex showed increased GLUT2 expression after incubation with the GR agonist dexamethasone (DEX) or norepinephrine (NE); DEX plus NE (DEX/NE) augmented GLUT2 in the female, but not in male. Glucoprivation did not alter GLUT2 expression, but eliminated NE regulation of this protein in both sexes. Male and female astrocyte glucokinase profiles were refractory to all drug treatments, but were down-regulated by glucoprivation. Glucoprivation altered AMPK expression in male only, and caused divergent sex-specific changes in activated, i.e., phosphoAMPK (pAMPK) levels. DEX or DEX/NE inhibited (male) or stimulated (female) AMPK and pAMPK proteins in both glucose-supplied and -deprived astrocytes. In male, NE coincidently up-regulated AMPK and inhibited pAMPK profiles in glucose-supplied astrocytes; these effects were abolished by glucoprivation. In female, AMPK profiles were unaffected by NE irrespective of glucose status, whereas pAMPK expression was up-regulated by NE only during glucoprivation. Present outcomes document, for each sex, effects of glucose status on hypothalamic astrocyte glucokinase, AMPK, and pAMPK protein expression and on noradrenergic control of these profiles. Data also show that DEX and NE regulation of GLUT2 is sex-monomorphic, but both stimuli impose divergent sex-specific effects on AMPK and pAMPK. Further effort is warranted to characterize mechanisms responsible for sex-dimorphic GR and noradrenergic governance of hypothalamic astrocyte energy sensory function.

Objectives Long-term isoflurane anesthesia exposure could result in postoperative cognitive dysfunction (POCD). Preoperative stress is also reported to be a risk factor of POCD. However, it is unknown whether acute stress could impair memory after long-term isoflurane anesthesia. Methods In this study, we categorized the mice with acute stress into mild (30 min restraint stress), moderate (60 min restraint stress), and severe (120 min restraint stress) stress groups and then we used Open-Field Test (OFT) to detect whether different scales of acute restraint stress successfully induced acute stress in mice. The memory performance of mice was measured using contextual and cued memory test, and the brain-derived neurotrophic factor protein levels of hippocampus was detected by Western blot. Results We verified that mild stress has pro-cognitive effect, but severe stress has amnestic effect. Moreover, we found that mild and moderate other than severe acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia. Conclusion Mild and moderate acute stress could partially attenuate the memory impairment induced by long-term isoflurane anesthesia.

As an intravenous anesthetic, propofol has been indicated to induce neurotoxicity in both animal and human brains. It is of great significance to better understand the potential mechanism of propofol-induced neurotoxicity to eliminate the side effects of propofol. Esketamine is a sedative that has been proven to have an antidepressant effect. However, its effect on propofol-induced neurotoxicity and the underlying mechanism remain unclear. Herein, we investigated the role of esketamine in propofol-induced brain injury. A rat model of propofol-induced brain injury was established with or without the treatment of esketamine. The results demonstrated that propofol-induced impairment in spatial learning and memory of rats and promoted oxidative stress, neuronal injury and apoptosis in rat hippocampal tissues. The effects caused by propofol were attenuated by esketamine. Esketamine activated the mature brain-derived neurotrophic factor/tropomyosin receptor kinase B/phosphatidylinositide 3-kinase (mBDNF/TrkB/PI3K) signaling pathway in propofol-administrated rats. Moreover, knocking down BDNF partially reversed esketamine-mediated activation of the mBDNF/TrkB/PI3K signaling pathway and inhibition of neuronal apoptosis in propofol-induced rats. Overall, esketamine mitigates propofol-induced cognitive dysfunction and brain injury in rats by activating mBDNF/TrkB/PI3K signaling.

Many diseases affect the autonomous nervous system and the central nervous system simultaneously, for example Parkinson’s disease or irritable bowel syndrome. To study neurophysiologic interactions between the intestinal electrical activity and the electroencephalography (EEG) pattern of the brain, we combined intestinal electrical stimulation (IES) and non-invasive telemetric full-band DC EEG recordings in an acute pig-model. Intestinal motility was monitored with accelerometers. Brain activity was analyzed with regard to network driven phenomena like phase amplitude coupling (PAC) within two time-windows: 1 min after IES (early response) and 3 min after stimulation (late response). Here we present the results for two stimulation sites (small intestine, colon) and two parietal scalp-EEG channels (right and left somatosensory cortex region). Electrical stimulation consisted of a 30 or 130 Hz pulse. In summary, the PAC modulation index at a parietal EEG recording position is decreased after IES. This effect is in line with an inhibitory effect of our IES protocol regarding peristalsis. The surprisingly strong effects of IES on network driven EEG patterns may be translated into new therapeutic techniques and/or diagnostic tools in the future. Furthermore, analytic tools, operating on sparse datasets, may be ideally suited for the integration in implantable intestinal pacemakers as feedback system.

Objective The aim of this study is to determine the personal and clinical factors that can predict recovery of motor function in people with stroke. Methods Characteristics of the study participants such as age, sex, time since stroke and type of stroke, motor function, shoulder pain, amount and quality of use of the affected limb in the real world, wrist and elbow spasticity, handedness, central post-stroke pain and dose of massed practice were recorded. The data obtained were analyzed using descriptive statistics and multiple regression. Results A total of 144 patients with stroke with mean age, 58.71 ± 19.90 years participated in the study. The result showed that, the whole model significantly explained the total variance by 88.4%, F (14, 144) = 32.870, R 2 = 0. 0.781, p < 0.001. However, in the final model, only four independent variables in the order of degree of predictability, amount of use of the limb in the real world (Beta = 0.455, p = 0.003), intensity of practice during rehabilitation session (Beta = 0.321, p < 0.001), wrist spasticity (Beta = 0.148, p = 0.004) and side affected (Beta = 0.093, p = 0.033) significantly predicted recovery of motor function. Conclusion Encouraging the use of the limb in the real world may be more important than practice during rehabilitation session in the clinic or in the laboratory.

Objective The purpose of this study was to investigate the significance of mismatch negativity (MMN) by comparing high-resolution electroencephalogram signals from tinnitus patients and healthy controls. Methods The study included eight subjects with chronic subjective idiopathic tinnitus and seven healthy controls. Participants with clinical speech (512–2,000 Hz) hearing thresholds less than 25 dB HL and with negative Hospital Anxiety and Depression Scale scores were included in the study. The E-Prime 2.0 software and a 256-electrode EGI Net Station system were used to evoke and record the MMN signal, and the amplitude and latency parameters of the MMN responses were compared between the two groups. Results From 150 ms, there was a significant difference between the amplitude of standard stimulation and deviation stimulation, and the event-related potential amplitude under deviation stimulation in the tinnitus patient group was significantly different from that in the healthy group. The MMN amplitude of the FCz electrode was statistically significantly lower in the tinnitus patients compared to healthy controls. Conclusion MMN has application value in the evaluation of abnormal electrical activity in the auditory pathway, and electroencephalograms are feasible for follow-up monitoring after acoustic therapy.

Recent evidence suggests no difference between patient outcomes when carotid endarterectomies (CEAs) are performed under general or regional anesthesia. However, for detecting the need for a shunt, general anesthesia has the drawback of monitoring needs in the intraoperative setting. In the present study, we attempted to perform intraoperative transcranial Doppler (TCD) monitoring for CEAs performed under intermediate plexus block to describe cerebral hemodynamic changes during different phases of the procedure. Patients and methods Patients with unilateral hemodynamically significant carotid stenosis scheduled for elective CEAs were included. Ultrasound-guided intermediate plexus block was used for regional anesthesia. TCD monitoring of the middle cerebral artery mean blood flow velocity (MCAV) was performed throughout the procedure. MCAVs were offline analyzed during different phases of CEA: (1) resting state, before regional block, (2) after block, before incision, (3) before cross-clamp, (4) after cross-clamp, (5) 5 min after cross-clamp, (6) 10 min after cross-clamp, (7) after declamping, and (8) during the postoperative period (4–6 h). Results Shunt insertion based on the deterioration of neurological symptoms after cross-clamping was necessary for 11/66 patients (16.6%). In these symptomatic patients, the ipsilateral percent decrease of the MCAV was more than 70% in 8 out of 11 cases (72.7%). In asymptomatic patients, without shunt insertion, the average decrease of MCAV was less than 50%. Conclusions Neurological symptoms referring to cerebral ischemia may be superior to TCD monitoring of cerebral blood flow for detecting the necessity of a shunt. Regional anesthesia enables reliable, symptom-based monitoring of CEAs.

Spinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI in mice. A model of SCI was established in C57BL/6 mice. The Basso Mouse Scale (BMS) score, BMS subscore, mechanical hypersensitivity, and thermal hypersensitivity of mice were tested for determining the motor function. Immunofluorescence staining was utilized to detect NeuN, GFAP, and Iba-1 levels in spinal cord tissues. ELISA was utilized to assess the contents of proinflammatory factors such as interleukin (IL)-1β, IL-18, and tumor necrosis factor-alpha (TNF-α) in spinal cord tissues. The levels of oxidative stress markers, reactive oxygen species, thiobarbituric acid-reactive substances, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were detected using their corresponding kits. Western blot was employed for estimating the levels of heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap-1). In this study, acacetin treatment recovered the motor function in SCI mice. Acacetin improved neuron integrity and repressed glial cell activation in the spinal cord tissues of SCI mice. Furthermore, acacetin administration reduced the SCI-induced high concentrations of IL-1β, IL-18, and TNF-α, as well as inhibited oxidative stress in SCI mice. Moreover, acacetin activated HO-1/Nrf2 pathway in SCI mice. The neuroprotective effects of acacetin against SCI were reversed by Nrf2 inhibitor. Overall, acacetin alleviated neuroinflammation and oxidative stress injury by activating the Nrf2/HO-1 signaling pathway in the mouse models of SCI.

Introduction Mitogen-activated protein kinase (MAPK) pathway is a major mechanism of acute brain damage in ischemic stroke. Pre-ischemic exercise is an effective method to reduce ischemic injury. However, the regulation by pre-ischemic exercise of MAPK pathway and associated mechanisms in animal models remains unclear. Materials and methods In this study, Male SD rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group, and exercise plus MCAO (EX + MCAO) group for 21 days, and then was established by MCAO. Longa score was used to measure neurological deficits at 0, 1, 2, and 3 days after MCAO. Hematoxylin and eosin staining was used to observe the brain injury. The expression of MAPK pathway was quantified by western blot. The M1 microglia protein was quantified by western blot and immunofluorescence, and the level of inflammatory factor was measured by enzyme-linked immunosorbent assay. TUNEL staining and western blot were used to measure apoptosis. Results In the current study, we observed that pre-ischemic exercise effectively decreased infarct volume, neurological deficit score and brain injury in MCAO rats through suppressing the activation of p-JNK and p-ERK1/2. Further investigation revealed that pre-ischemic exercise decreased M1 microglia activation and the serum level of TNF-α and IL-1β. In addition, the increased number of TUNEL-positive cells and Bax/Bcl-2 ratio also were reversed by pre-ischemic exercise. Conclusions Pre-ischemic exercise can alleviate inflammatory response and apoptosis by inhibiting the MAPK pathway in MCAO rats.

Successful recognition has been known to produce distinct patterns of neural activity. Many studies have used spectral power or event-related potentials of single recognition-specific regions as classification features. However, this does not accurately reflect the mechanisms behind recognition, in that recognition requires multiple brain regions to work together. Hence, classification accuracy of subsequent memory performance could be improved by using functional connectivity within memory-related brain networks instead of using local brain activity as classifiers. In this study, we examined electroencephalography (EEG) signals while performing a word recognition memory task. Recorded EEG signals were collected using a 32-channel cap. Connectivity measures related to the left hemispheric fronto-parietal connectivity (P3 and F3) were found to contribute to the accurate recognition of previously studied memory items. Classification of subsequent memory outcome using connectivity features revealed that the classifier with support vector machine achieved the highest classification accuracy of 86.79 ± 5.93% (mean ± standard deviation) by using theta (3–8 Hz) connectivity during successful recognition trials. The results strongly suggest that highly accurate classification of subsequent memory outcome can be achieved by using single-trial functional connectivity.

Depression has become one of the most crucial public health issues, threatening the quality of life of over 300 million people throughout the world. Nevertheless, the clinical diagnosis of depression is now still hampered by behavioral diagnostic methods. Due to the lack of objective laboratory diagnostic criteria, accurate identification and diagnosis of depression remained elusive. With the rise of computational psychiatry, a growing number of studies have combined resting-state electroencephalography with machine learning (ML) to alleviate diagnosis of depression in recent years. Despite the exciting results, these were worrisome of these studies. As a result, ML prediction models should be continuously improved to better screen and diagnose depression. Finally, this technique would be used for the diagnosis of other psychiatric disorders in the future.

Health behaviors during pregnancy have an impact on the developing offspring. Dietary factors play a role in the development of mental illness: however, less is known about the impact of diet factors during pre-conception, gestation, and lactation on anxiety levels in offspring. This scoping review sought to systematically map the available research involving human and animal subjects to identify nutritional interventions which may have a harmful or protective effect, as well as identify gaps. Studies investigating an association between any perinatal diet pattern or diet constituent and offspring anxiety were included. The number of studies reporting an association with increased or decreased levels of anxiety were counted and presented in figures. A total of 55,914 results were identified as part of a larger scoping review, and 120 articles met the criteria for inclusion. A greater intake of phytochemicals and vitamins were associated with decreased offspring anxiety whereas maternal caloric restriction, protein restriction, reduced omega-3 consumption, and exposure to a high fat diet were associated with higher levels of offspring anxiety. Results were limited by a very large proportion of animal studies. High quality intervention studies involving human subjects are warranted to elucidate the precise dietary factors or constituents that modulate the risk of anxiety in offspring.

Studies of pathophysiological mechanisms involved in eating disorders (EDs) have intensified over the past several years, revealing their unprecedented and unanticipated complexity. Results from many articles highlight critical aspects in each member of ED family. Notably, anorexia nervosa (AN) is a disorder due to undefined etiology, frequently associated with symptoms of depression, anxiety, obsessive-compulsiveness, accompanied by endocrine alterations, altered immune response, increased inflammation, and dysbiosis of the gut microbiota. Hence, an advanced knowledge of how and why a multisystem involvement exists is of paramount importance to understand the pathogenetic mechanisms of AN. In this review, we describe the change in the brain structure/function focusing on hypothalamic endocrine disorders and the disequilibrium of gut microbiota in AN that might be responsible for the psychopathological complication.

Approximately 6.8 million people die annually because of problems related to the central nervous system (CNS), and out of them, approximately 1 million people are affected by neurodegenerative diseases that include Alzheimer’s disease, multiple sclerosis, epilepsy, and Parkinson’s disease. CNS problems are a primary concern because of the complexity of the brain. There are various drugs available to treat CNS disorders and overcome problems with toxicity, specificity, and delivery. Barriers like the blood–brain barrier (BBB) are a challenge, as they do not allow therapeutic drugs to cross and reach their target. Researchers have been searching for ways to allow drugs to pass through the BBB and reach the target sites. These problems highlight the need of nanotechnology to alter or manipulate various processes at the cellular level to achieve the desired attributes. Due to their nanosize, nanoparticles are able to pass through the BBB and are an effective alternative to drug administration and other approaches. Nanotechnology has the potential to improve treatment and diagnostic techniques for CNS disorders and facilitate effective drug transfer. With the aid of nanoengineering, drugs could be modified to perform functions like transference across the BBB, altering signaling pathways, targeting specific cells, effective gene transfer, and promoting regeneration and preservation of nerve cells. The involvement of a nanocarrier framework inside the delivery of several neurotherapeutic agents used in the treatment of neurological diseases is reviewed in this study.

Background Hepatolenticular degeneration (HLD), also known as Wilson disease (WD), is a rare autosomal-recessive hereditary disease, which is often missed and misdiagnosed because of its various clinical manifestations. And WD is even more rare with giant subarachnoid cysts. In this report, we will provide a case of WD with an intracranial arachnoid cyst (IAC). Case description A 27-year-old woman was hospitalized in a traditional Chinese medicine hospital in Guangzhou with the first manifestation of a “slight involuntary tremor of her left upper limb”. There was no improvement after acupuncture treatment, and then she was transferred to another large general hospital in Guangzhou. MRI examination of the head showed “left frontal, parietal and temporal giant subarachnoid cyst” and the patient underwent “left frontotemporal arachnoid cyst celiac shunt operation.” After the operation, the patient’s left limb shaking remained unchanged. Subsequently, the patient was referred to another big hospital in Guangzhou, considered “Parkinson’s disease,” and given “Medopa, Antan” and other treatments. However, the patient’s limb shaking continued to increase and gradually developed to the extremities. At last, the patient was referred to our hospital, combined with the medical history, neurological signs, and auxiliary examination results, improve the examination of corneal K-F ring, blood ceruloplasmin, gene screening, and other tests; the diagnosis was confirmed as hepatolenticular degeneration. Conclusion After expelling copper and symptomatic treatment, the condition is improved.

Background To date, only 25 cases of cerebral infarction following a bee or wasp sting have been reported. Due to its rarity, undefined pathogenesis, and unique clinical features, we report a case of a 62-year-old man with progressive cerebral infarction following bee stings, possibly related to vasospasm. Furthermore, we review relevant literature on stroke following bee or wasp stings. Case presentation A 62-year-old retired male presented with progressive ischemic stroke after bee stings to the ear and face. Initial magnetic resonance imaging of the brain showed small punctate infarcts in the left medulla oblongata. Head and neck computed tomography angiography showed significant stenosis in the basilar artery and occlusion in the left V4 vertebral artery. The patient received intravenous alteplase (0.9 mg/kg) without symptomatic improvement. Digital subtraction angiography later demonstrated additional near occlusion in the left posterior cerebral artery (PCA). Thrombectomy was considered initially but was aborted due to hemodynamic instability. Repeated CT brain after 24 h showed acute infarcts in the left parieto-occipital region and left thalamus. The near occluded PCA was found to be patent again on magnetic resonance angiography (MRA) 25 days later. This reversibility suggests that vasospasm may have been the underlying mechanism. Unfortunately, the patient had persistent significant neurological deficits after rehabilitation one year later. Conclusion Cerebral infarction following bee stings is rare. There are several proposed pathophysiological mechanisms. While the natural course of this phenomenon is not well characterized, early diagnosis and treatment are essential. Furthermore, it is important to establish standardized care procedures for this unique entity.

Neurosarcoidosis is an uncommon and multiform clinical entity. Its presentation as an isolated longitudinal extensive transverse myelitis (LETM) is rare and challenging to identify. We report a case of LETM in a 60-year-old patient with no significant systemic symptoms nor relevant medical history. The peculiar spinal magnetic resonance imaging finding characterized by a posterior and central canal subpial contrast enhancement, the so-called “trident sign,” together with chest computed tomography scan and lymph node biopsy led to the diagnosis of sarcoidosis. We also discuss the main differential diagnoses of LETM and therapeutic options for sarcoidosis-related myelitis.

Introduction Ekbom Syndrome (ES) is characterised by fixed, delusional beliefs that one’s body is infested by parasites or other vermin in absence of supporting clinical evidence. Antipsychotic (AP) treatment, including long-acting injectable (LAI) AP in subjects with poor compliance, is prescribed to manage behavioural and psychotic symptomatology. Objectives We describe a 70-year-old woman who was hospitalised after experiencing new-onset delusions of infestation with visual and tactile hallucinations that led to bizarre behaviours and progressive social withdrawal. Methods She was diagnosed with ES and was initially treated with risperidone 3 mg; however, due to poor compliance and a lack of insight, she was switched to LAI palmitate paliperidone (LAI-PP). She was followed up for 8 months, administering Positive and Negative Syndrome Scale, Montreal Cognitive Assessment, Global Assessment of Functioning, Brief Psychiatric Rating Scale, neurocognitive assessment, and neuroimaging. Results After a progressive cognitive deterioration, she was diagnosed with an ES secondary to Lewy body dementia (DLB). Conclusion The LAI-PP treatment determined a complete clinical remission of psychotic symptoms despite the emergence of an iatrogenic akinetic-rigid syndrome. The delay of confirmatory neurological diagnosis, the associated risky behaviours of the patient, and poor treatment adherence led clinicians to prescribe LAI-PP following a good clinical response to oral paliperidone. However, in the case of a suspected DLB diagnosis, the prescription of an LAI-PP as a first-line strategy should be carefully evaluated.

A possible association between Bell’s palsy and COVID-19 vaccination has been suggested. While it is likely that COVID-19 vaccine recipients from the general population do have a slightly increased risk of developing Bell’s palsy, there are little data regarding this risk in individuals with a history of disease. Gaining a better understanding of this association is particularly important for informing evidence-based recommendations regarding future booster shots in subjects who developed Bell’s palsy as a side effect of vaccination, or as a result of SARS-CoV-2 infection. We previously described the first case of COVID-19 vaccine-related Bell’s palsy; here we report an 18-month clinical and electromyographic follow-up and discuss the implications of receiving further vaccine doses in patients with positive disease history.

Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by severe sleep-related rigid hypermotor seizures. The pathogenic genes of ADSHE include genes encoding subunits of the neuronal nicotinic acetylcholine receptor, KCNT1 , DEPDC5 , NPRL2/3 , CABP4 , and CRH. Individuals with KCNT1 -related ADSHE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems. In this study, a 12-year-old Chinese girl was referred for genetic evaluation of grand mal seizures. She had paroxysmal convulsions of the limbs and loss of consciousness just after falling asleep without obvious triggers. A novel heterozygous missense mutation c.2797C > T (p.Arg933Cys) in exon 24 of the KCNT1 was identified in the proband by whole-exome sequencing and Sanger sequencing, and the clinical symptoms were compatible with ADSHE. The proband’s father has been showing similar symptoms for more than 20 years and had the same site mutation. Her mother and sister were physically and genetically normal. The study revealed a novel variant in the KCNT1 and expanded the mutation spectrum for this clinical condition. Our results provide further evidence supporting a causative role in KCNT1 variants in ADSHE.

Background Anaplastic astrocytoma (AA) is rarely observed in the brainstem and the clinical symptoms and imaging manifestations vary, which present a great challenge to accurate clinical diagnosis. Case description A 56-year-old woman, with a month-long history of nausea and vomiting, was first diagnosed with acute cerebral infarction and demyelinating disease. The patient showed negative results on enhanced magnetic resonance and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography, and the clinical symptoms were not typical, leading to early misdiagnosis. Conclusion Finally, the patient was diagnosed with AA by pathological biopsy.

Introduction Rare and mild adverse effects on cranial nerves have been reported after vaccination. Here, we report a singular case of smell and taste disorder associated with tinnitus that occurred after Oxford-AstraZeneca vaccination together with a review of the available literature. Case presentation A 76-year-old patient experienced smell disorder, ear fullness and tinnitus 2 days after the first dose of Oxford-AstraZeneca vaccine. The patient then underwent a complete audiological and Ear, Nose and Throat evaluation, nasal endoscopy, Sniffin’Sticks battery, audiometric test battery, and cerebral magnetic resonance imaging (MRI). The exams revealed hyposmia and bilateral reduction of the volume of the olfactory bulbs (OB). At the follow-up, tinnitus was completely resolved while olfactory dysfunction only partially reduced. Review of the literature A PubMed search was conducted on olfactory and gustatory dysfunctions after COVID-19 vaccination resulting in four case reports with a total of 10 patients. The main symptoms were hyposmia, parosmia, and dysgeusia developed after 1–9 days from vaccination with complete resolution occurring within 1 month. Notably, none of the considered articles reported reduction of OB volumes at cerebral MRI. Discussion So far, no definitive cause–effect relationship has been established between anti-COVID19 vaccination and otolaryngologic adverse reactions. The persistence of hyposmia in our patient could possibly be explained by the reduction in OB volume, even though also the advanced age of the patient needs to be taken into account. This is a first indication of a cause–effect relation between hyposmia and Covid19 vaccination, even though a more robust study is needed to confirm the autoimmunological mechanisms responsible for these rare adverse reactions. However, it is worth highlighting that benefits of the anti-COVID-19 vaccination clearly outweigh the risk of rare adverse events.

Lymphoplasmacyte-rich meningioma (LPRM) is a rare subtype of meningioma, the specific pathogenesis of which remains unclear. Herein, we report the case of a 48-year-old Asian man who experienced progressive deafness and limb weakness. Magnetic resonance imaging revealed extramedullary masses diffusely growing, wrapping, and compressing the cervical spinal cord. The dural lesion was partially excised by surgery, and postoperative pathological examination confirmed the diagnosis of LPRM. Diffuse LPRM is extremely rare, and its treatment is challenging owing to difficulties associated with surgery and the uncertain efficacy of traditional therapies. Therefore, further clinical practice and basic research are needed to improve the prognosis of diffuse LPRM.

Depression is a common mood disorder characterised by high comorbidity with other mental and somatic diseases. New studies reveal a shared genetic base for mental core symptoms and somatic comorbidities. Functional analyses showed multiple brain–body pathways involved. This may help considering new therapeutic approaches for depression as a system’s disorder.

The precise pathogenesis of achalasia is still unclear. Neurodegenerative and/or demyelinating disorders (NDD) appear to share some common pathophysiological pathways described in achalasia such as inflammation, autoimmune, mitochondrial dysfunction, and neurodegeneration. Jerie et al. have published on the October issue a prospective study assessing the prevalence of several NDD in achalasia patients. In this commentary, we shed some light on the possible link between achalasia and NDD as well as comment on the study by Jerie et al.

We report a 30-year-old man involving gastrointestinal symptoms, vitreous opacity, and multiple cranial neuropathies. Transthyretin-related hereditary amyloidosis genetic testing revealed a rare c.251T > C variant p.(Phe84Ser). Only four cases with this variant have been reported before.