Volume 16, Issue 1

Objective To analyze the effect of gradient thrombectomy stent in vitro . Methods The cerebrovascular fluid circulation model was made and fixed on the test table. About 0.9% sodium chloride injection was injected to the vascular model through a miniature water pump to circulate it. Four kinds of thrombus products containing different red blood cell (RBC) volumes of 0, 5, 40, and 80% were placed at the target location as thrombus. Each type of thrombus was removed five times using SOLITAIRE stent and gradient thrombectomy stent. The thrombectomy effects were observed by comparison of the two types of stents. Results Thrombus containing 80% volume of RBC escaped thrombus fragments during thrombectomy with both stents. Thrombus containing 0% volume of RBC (rich in fibrin) had poor chimerism with stents. In the thrombus containing 0% RBC volume, there was no statistically significant difference between the two stents ( p = 1). Thrombus removal was successful in all cases. Conclusion The gradient thrombectomy stent is as effective as the currently used thrombectomy stent in vitro studies, and there is much room for improvement.

Interest in the societal and psychological harm caused by widespread envy and social comparison is increasing. Envy is associated with anxiety and depression, though the mechanism by which envy affects neuropsychiatric disorders, such as depression, remains unclear. Clarifying the neurobiological basis of envy’s effects on behaviour and emotion regulation in experimental mice is essential for developing disease-prevention and treatment strategies. As mice recognize other mice in neighbouring cages, this study investigated whether they recognize neighbouring cages housed in environmentally enriched cages and suffer psychological stress due to envy. After being raised in an envy-like environment for 3 weeks, we revealed changes in the behaviour of the mice through a series of behavioural experiments. Mice raised in an envious environment showed increased body weight and anxiety-like behaviour but decreased social behaviour and serum corticosterone levels compared to control mice. Thus, mice recognize their neighbouring cages and experience psychological stress due to envy. This study revealed a part of the scientific basis for why envy increased anxiety. Using this novel experimental breeding environment, it may be possible to create an experimental animal model of anxiety disorders.

Spontaneously hyperlipidaemic (Apoe shl ) mice were discovered in 1999 as mice lacking apolipoprotein E (ApoE) owing to a mutation in the Apoe gene. However, age-related behavioural changes in commercially available Apoe shl mice have not yet been clarified. The behavioural abnormalities of ApoE-deficient mice, which are genetically modified mice artificially deficient in ApoE, have been investigated in detail, and it has been reported that they can serve as a model of Alzheimer’s disease (AD). To understand whether Apoe shl mice can also serve as a murine model of AD, it is necessary to investigate age-related behavioural abnormalities in Apoe shl mice. In this study, we conducted a series of behavioural experiments on 7- and 11-month-old Apoe shl mice to investigate the behavioural abnormalities associated with ageing in Apoe shl mice. In this study, 7-month-old Apoe shl mice showed decreased body weight and grip strength compared to age-matched wild-type mice. In the open field test, 7-month-old Apoe shl mice showed increased anxiety-like behaviour compared to wild-type mice, whereas 11-month-old Apoe shl mice showed decreased anxiety-like behaviour. Moreover, Apoe shl mice aged 7 and 11 months had increased serum cholesterol levels. These results indicate that the behaviour of Apoe shl mice changes with age. However, 11-month-old Apoe shl mice did not show a decline in cognitive function or memory ability similar to murine models of AD. Our findings indicate that Apoe shl mice can be used to investigate the function of ApoE in the central nervous system.

Parkinson’s disease (PD), a neurodegenerative disorder characterized by degeneration of the dopaminergic (DA) neurons, is still lack of available treatments to completely block neurodegeneration. (−)-Epigallocatechin-3-gallate (EGCG), a predominant active polyphenol generated from green tea, exerts multiple neuroprotective roles in the nervous system. However, the function role of EGCG in PD and the underlying mechanism remains to be investigated. In the current study, we used the rotenone injection to build the PD rat model, followed by the EGCG treatment and determined by the behavior tests, measurements of malondialdehyde, glutathione, and superoxide dismutase levels, and enzyme-linked immunosorbent assay. We revealed that, in PD rats, EGCG upregulates protein kinase D1 (PKD1) and inhibits Parthanatos to ameliorate the impaired motor function, reduce the expression of tyrosine hydroxylase, suppress the oxidative stress, and suppress the inflammation in substantia nigra. These combined results suggest that EGCG can suppress oxidative stress and inflammation to prevent DA neuron degeneration to prevent rotenone-induced motor impairments, laying the foundation for EGCG to be a novel candidate for the treatment of PD.

Spinal cord injury (SCI) seriously affects the health of humans and quality of life, causing disabilities. Due to the ever-increasing traffic and cases of natural disasters, such as earthquakes, the incidence of SCI increases every year, thus causing a huge economic burden to society and patients. The lack of neurotrophic factors in the area affected by SCI and the presence of inhibitory factors for axonal regeneration are important reasons that make spinal cord regeneration and repair extremely difficult. Additionally, the correct projection of axons also plays an important role. As Netrin-1 is a signaling factor that guides axon growth, in this study, to determine whether Netrin-1 can promote axonal regeneration after binding to the receptor DCC following SCI, a Netrin-1/DCC co-expression recombinant lentiviral vector was constructed. This vector was used to assess the effect of Netrin-1 on the NgR1-RhoA-ROCK signaling pathway in an SCI model constructed in this study. Our results suggested that Netrin-1 exerts neuroprotective effects by inhibiting the NgR1-RhoA-ROCK signaling pathway after binding to its receptor DCC.

Objective Cannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study. Methods We evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral, and injection (intraperitoneal) routes. We used CBD broad spectrum (inhaled and intraperitoneal) vs CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups. Results Our findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested, CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures ( p < 0.05) compared to other forms of CBD treatments. Conclusion Our data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, which warrants further research.

Background Unruptured intracranial aneurysms (IAs) are increasingly detected due to advancements in neuroimaging. Despite improvements in treatment, aneurysmal subarachnoid haemorrhage (aSAH) is associated with high mortality and morbidity. Treatment decisions for IA are complex and individualized, considering aneurysm and patient-related risk factors. Genetic factors, particularly endothelial nitric oxide synthase (eNOS) polymorphisms, have been implicated in IA formation and rupture risk. Methods This study investigated the association between three eNOS polymorphisms (27-bp-VNTR, T786C, and G894T) and aSAH in a cohort of 275 patients with unruptured IA or aSAH. Patients were followed for at least 8 years with clinical and imaging assessments. Genotyping of selected polymorphisms was performed, and statistical analyses were conducted to identify interactions between genetic polymorphisms and established risk factors. Results A significant difference in the frequencies of genotypes and allele carriers of the T786C polymorphism was observed between patients with unruptured IA and those with aSAH, with an increased proportion of CC homozygotes in the aSAH group. The risk of rupture was higher in patients with the CC genotype. Multilobular aneurysms and those located in the posterior circulation had a higher incidence of rupture. Associations between arterial hypertension and certain genotypes were also found. However, no significant interaction was observed between the polymorphisms and established risk factors in relation to aneurysm rupture. Conclusion Our data showed a significant and independent correlation between eNOS genetic polymorphism T786C and aSAH.

Background Within the last few decades, the domestic pig has emerged as an advantageous biomedical animal model due to a vast number of similarities in realms of development and neuroanatomical features. Even so, a major challenge remains in how to translate time between the pig and human. Previously, researchers have developed a Translating Mammalian Time model that estimates the timing of 95 neurodevelopmental events across 9 mammalian species. By identifying the timing of these various events, one can include an additional animal into the model and assign a unique species score to predict the post-conception day (PCD) that other events will occur. Objective Our objective was to conduct a comprehensive literature review of pig neurodevelopmental events to enable chronological comparison to other mammalian species, including humans. Methods A total of 30 neurodevelopmental events with corresponding PCDs were identified, that were then used to optimize the pig’s species score using grid search and gradient descent approaches. Results and Conclusion Across both methods, the same species score of 2.157 was derived with a residual sum of squares of 4260.46. This species score places the domestic pig between the cat (1.808) and the macaque (2.255), thereby reinforcing the translational power of the pig comparable to non-human primates.

Background Several findings indicate that stress may influence epileptiform discharges manifesting in temporal-limbic areas, which may become a potential trigger of psychosis that may manifest without neurologically diagnosed epilepsy. Some findings suggest that measures assessing levels of inter-hemispheric information connection may reveal the spread of subclinical epileptiform neural activity associated with psychotic and seizure-like symptoms. Recent research also suggests that electrodermal activity (EDA), which is related to limbic activations, may allow indirect measurement of interhemispheric information transmission. These findings about the interhemispheric spread of information suggest a hypothesis that heightened spread of information between the brain hemispheres might indirectly indicate epileptiform discharges spreading between hemispheres. Methods We have analyzed and measured EDA and also cognitive and affective epileptic-like symptoms (CPSI, complex partial seizure-like symptoms), symptoms of chronic stress (Trauma Symptoms Checklist-40, TSC-40), and psychotic symptoms in 31 schizophrenia patients and compared these data with 31 healthy controls. Results The results indicate that in schizophrenia patients, the values of pointwise transinformation (PTI) calculated from right and left EDA time series are related to CPSI symptoms (Spearman correlation between CPSI and PTI is R = 0.48; p < 0.01) and symptoms of chronic stress (Spearman correlation between TSC-40 and PTI is R = 0.37, p < 0.05); both during mild stress conditions caused by conflicting (incongruent) Stroop task. Conclusion The analysis indicates potentially diagnostically useful results suggesting that heightened PTI values may reflect autonomic activations that hypothetically might be linked to higher interhemispheric transmission related to spreading of epileptiform discharges between hemispheres.

Estradiol shapes systemic glucose homeostasis by action on ventromedial hypothalamic nucleus (VMN) targets. The neuropeptide transmitter growth hormone-releasing hormone (Ghrh) governs counterregulatory neurochemical marker mRNA expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1/Nr5a1) neurons. The current research used tools for in vivo gene silencing and single-cell laser catapult microdissection/multiplex qPCR to determine if VMN Ghrh receptor (Ghrh-R) regulates nuclear and/or membrane estrogen receptor (ER) gene transcription in those neurons. Intra-VMN Ghrh-R siRNA correspondingly up- or down-regulated baseline VMNdm Ghrh/SF-1 neuron ER-alpha (ERα) or G protein-coupled estrogen receptor-1 (GPER) transcripts in male rats; neither mRNA was affected by gene silencing in females. In each sex, hypoglycemic repression of these ER gene profiles was averted by Ghrh-R gene knockdown. Both sexes exhibited diminished baseline VMNdm Ghrh/SF-1 neuron ER-beta (ERβ) gene expression following Ghrh-R gene knockdown. ERβ mRNA was diminished (male) or unaffected (female) by hypoglycemia; Ghrh-R siRNA pretreatment enhanced transcript levels in hypoglycemic rats of either sex. Aromatase gene expression is higher in male versus female VMNdm Ghrh/SF-1 neurons and is inhibited by hypoglycemia in male rats alone. Ghrh-R gene knockdown augmented aromatase mRNA levels in each sex irrespective of glucose status. Results document glucose-dependent Ghrh-R control of VMNdm Ghrh/SF-1 neuron ERα (female), ERβ (both sexes), and GPER (both sexes) gene expression. Ongoing studies aim to characterize mechanisms that cause a hypoglycemia-associated gain of regulatory control or switch in direction (stimulatory-to-inhibitory) of control. Outcomes identify VMNdm Ghrh/SF-1 neurons as a putative neuroestradiol source in each sex and implicate Ghrh-R in hypoglycemic repression of this neurosteroid profile in males.

Background Depression is a pervasive neuropsychiatric disorder having significant social and economic impacts and often linked to imbalances in neurotransmitter systems. Traditional herbal medicines have garnered attention for their potential antidepressant effects, with limited research on Helianthus annuus (sunflower) as a therapeutic option. Objectives The present study was carried out to investigate the anti-depressant and neuromodulatory potential of hydroalcoholic extract of Helianthus annuus ( H. annuus ) florets in mouse models of depression. Methods Depression was induced in rats by the forced swim test (FST) and tail suspension test (TST). The hydroalcoholic extract of H. annuus was used as the test drug given in the doses of 200 and 400 mg/kg, whereas fluoxetine was used as the standard drug. Results The results revealed that the H. annuus extract decreased the immobility time significantly as reflected in FST and TST. Treatment with H. annuus extract also demonstrated significant improvement in the swimming and climbing times as reflected in FST. Administration of H. annuus extract significantly improved neurotransmitter levels such as serotonin, dopamine, and norepinephrine, which were significantly lowered in depression control rats. The mean value of thiobarbituric acid reactive substances was significantly lowered after the administration of H. annuus extract. Additionally, the levels of glutathione, superoxide dismutase, and catalase were significantly increased after the administration of H. annuus extract. Additionally, the mean value of inflammatory cytokines, for example, tumour necrosis factor alpha and interleukin-6 were reduced significantly in groups treated with H. annuus extract. Conclusions The results suggest that H. annuus extract exhibited significant antidepressant and neuromodulatory potential by ameliorating behavioural parameters, oxidative stress, and inflammatory markers. Graphical abstract

Objective This study aims to determine if Lycium barbarum polysaccharides (LBP) extract attenuate oxidative stress by regulating the SIRT1/PGC-1α axis, potentially ameliorating oxygen–glucose deprivation/reperfusion (OGD/R)-induced neuronal damage. Methods A cellular hypoxia/reoxygenation model (OGD/R) using HT22 cells was established to simulate cerebral ischemia–reperfusion injury. Cells were allocated into four groups: normal (Control), hypoxia (OGD/R), LBP extract-treated (OGD/R + LBP at 25, 50, 100 μg/mL), and SIRT1-inhibited (OGD/R + S100). Western blot and qPCR were performed to detect the expression of pathway-related factors, oxidative stress, mitochondrial function, and apoptosis-related factors. Results Compared to the Control group, the OGD/R group exhibited significantly reduced cell survival, increased LDH release, apoptosis rate, and reactive oxygen species (ROS) levels. After intervention with LBP extract, cell survival increased, LDH release, ROS levels, and apoptosis rates reduced. The above injuries were associated with the inhibition of the SIRT1/PGC-1α pathway. LBP extract can attenuate the hypoxia-reperfusion-induced inhibition of the SIRT1/PGC-1α pathway and reverse the resulting high levels of oxidative stress and apoptosis, ultimately ameliorating cellular injury. Conclusion LBP extract’s protective effects against ischemia–reperfusion injury in HT22 cells appear linked to the modulation of the SIRT1/PGC-1α pathway and a reduction in oxidative stress.

Background Multiple sclerosis (MS) is a major demyelinating disorder that affects the central nervous system. A growing body of evidence has revealed the involvement of coagulation pathway in the pathogenesis of MS. However, the causal association between coagulation factors and MS is still unclear. Method A two-sample Mendelian randomization (MR) analysis was conducted. Genetic variants for plasma coagulation factors were identified as instrumental variables. Summary-level statistics for MS were collected from a large-scale genome-wide association study, including 47,429 cases and 68,374 controls. Primary MR analysis was performed using the inverse-variance weighting (IVW) approach. False discovery rate (FDR)-adjusted method was applied to adjust for multiple testing. MR-Egger, weighted median, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as sensitivity analysis approaches. Results A causal effect of higher plasma tissue factor (TF) levels on the risk of MS onset was identified using IVW method (OR: 1.215, 95% CI 1.108–1.333, P < 0.001, P FDR < 0.001). Complementary analysis using weighted median (OR: 1.262, 95% CI: 1.119–1.423, P < 0.001), weighted mode (OR: 1.238, 95% CI: 1.100–1.394, P = 0.012), and MR-PRESSO (OR: 1.215, 95% CI: 1.125–1.313, P = 0.003) methods yielded consistent results. Null associations were found for other plasma coagulation factors with MS. Conclusions The study demonstrates a suggestive association between TF and MS. Increasing plasma TF was associated with an increase in MS risk. TF should be a promising biomarker and new target for MS.

Background As a non-competitive blocker of the N -methyl- d -aspartate receptor, ketamine is widely used for anesthesia and pain relief in clinical settings. However, certain neurological side effects may appear if it is used for the long term. According to clinical observations, anesthetic doses of ketamine trigger postoperative neurocognitive dysfunction in elderly patients, while subanesthetic doses of ketamine suppress the postoperative neuronal pyroptosis in the hippocampus, ameliorating the cognitive function. There is a certain link between brain and muscle arnt-like 1 (Bmal1) and the postoperative cognitive functions of elderly patients. Meanwhile, the Bmal1 activity can be intensified by subanesthetic doses of ketamine. How subanesthetic doses of ketamine act on the postoperative cognitive functions of elderly patients via Bmal1 is to be further investigated. Methodology To expound how different doses of ketamine affect the cognitive functions of 15-month-old mice (No.: C57BL/6) receiving partial hepatectomy (PH), the following assays were conducted: (1) Morris Water Maze tests were made on mice on days1, 3, and 7 post-surgery; (2) histopathological analyses (by Nissl and Tunel staining) as well as western blotting, immunofluorescence, immunohistochemical, and ELISA assays were carried out on the hippocampal tissue samples collected from the mice 3 days post-surgery. Furthermore, to verify the critical role of the Bmal1 gene in the subanesthetic doses of ketamine-based improvement of cognitive function in aged mice post-surgery, the survey on 15-month-old mice (No.: C57BL/6) with inactivated Bmal1 gene was continued. Through the aforementioned assays, the modulation mechanism of subanesthetic doses of ketamine in ameliorating postoperative cognitive functions of aged mice was elucidated. Results As revealed through this investigation, subanesthetic doses of ketamine compared with the sham group effectively enhanced mice’s memory and learning ability, increased the expression of p-NR2B and BDNF proteins, mitigated neuronal pathologic injuries and neuroinflammation in aged mice post-surgery, upregulated the gene expression of Bmal1, and inhibited the hippocampal neuronal pyroptosis mediated by the NF-κB/NLRP3 signaling pathway. These effects are contrary to those of anesthetic doses of ketamine. Furthermore, for mice with an inactivated Bmal1 gene, injecting subanesthetic doses of ketamine helped to alleviate neuronal pathological injuries and neuroinflammation in the hippocampal tissues, suppress the expression of cytokines pertaining to the NF-κB/NLRP3 signaling pathway, and improve postoperative memory and learning competence of the mice. Conclusion Subanesthetic doses of ketamine can elevate the expressed level of Bmal1, dampening the NF-κB/NLRP3 pathway-mediated cell pyroptosis, alleviating neuroinflammation, and improving the postoperative cognitive functions of aged mice. The findings in this study suggest a novel approach to explore using subanesthetic doses of ketamine to ameliorate the cognitive functions of aged patients post-surgery and clinically prevent postoperative neurocognitive disorders. Graphical abstract Subanesthetic dose of ketamine can alleviate pyroptosis and neuroinflammation mediated by the NF-κB/NLRP3 pathway via upregulating Bmal1 expression, thereby alleviating cognitive function after partial hepatectomy in elderly mice.

Objectives Excessive neuroinflammatory responses represent a key pathological mechanism in cerebral small vessel disease (CSVD). Dl-3- n -butylphthalide (NBP), a compound previously demonstrated to possess anti-inflammatory properties in ischemic stroke, was investigated for its potential therapeutic effects in a rodent model of CSVD. This study aimed to elucidate the neuroprotective mechanisms of NBP in CSVD pathogenesis. Methods Forty-week-old spontaneously hypertensive rats were selected as a CSVD rodent model to determine the neuroprotective effects of NBP. Cognitive ability was assessed using the Morris water maze after 28 weeks of treatment. Pathological changes in the brain tissue were observed through immunohistochemistry. Data-independent acquisition (DIA) mass spectrometry was executed to identify the probable targets of NBP in CSVD. Based on the proteomics results, the expression of the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway in the rat hippocampus was evaluated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). Results NBP treatment ameliorated the cognitive abilities and pathological changes in CSVD. DIA proteomics revealed 262 differentially expressed hippocampal proteins, with bioinformatics analysis highlighting acute inflammatory response as a primary target. Furthermore, western blotting and qRT-PCR results confirmed these results and showed that after treatment with NBP, TLR4 regulated NF-κB pathway and inflammatory factors decreased. Conclusions Our findings demonstrated that NBP exerts neuroprotection in CSVD probably by suppressing TLR4/MyD88/NF-κB-mediated neuroinflammation. This study provides the evidence of NBP’s therapeutic mechanisms in CSVD, suggesting its potential as a targeted anti-inflammatory treatment.

Objective Acute sleep deprivation (ASD) is prevalent in contemporary society. This study explored the mechanism of melatonin affecting cognitive dysfunction (CD) in ASD mice through the nuclear factor kappaB (NF-κB) pathway and oxidative stress. Methods The ASD mouse model was established and treated with low-dose and high-dose melatonin, a NF-κB inhibitor PDTC, or lipopolysaccharide (LPS), with their spatial memory, spontaneous activity, and anxiety assessed. Hippocampal morphology and neuronal status were observed via HE and Nissl staining. Superoxide dismutase (SOD) activity and levels of hippocampal CA1 region postsynaptic density protein 95 (PSD95), phosphorylated (p)-p65, and p-IκB proteins; acetylcholinesterase (AChE), acetylcholine (ACh), malondialdehyde (MDA), and reactive oxygen species (ROS); and IL-4, IL-10, tumor necrosis factor [TNF]-α, and IL-1β levels were determined by western blot and ELISA kits. Results ASD mice exhibited reduced learning and memory abilities and spontaneous activities, loosely-arranged cells in the hippocampal CA1 region, unclear cell body boundaries, enlarged gaps, severe neuronal damage, and reduced PSD95 protein level. There were increases in AChE, p-p65, p-IκB, TNF-α, IL-1β, MDA, and ROS levels, decrements in ACh, IL-4, and IL-10 levels and SOD activity in the hippocampal CA1 region of ASD mice. Melatonin or PDTC inhibited the NF-κB pathway, down-regulated TNF-α, IL-1β, MDA, and ROS and up-regulated IL-4 and IL-10 and SOD activity in the hippocampal CA1 region of ASD mice, and improved the learning and memory abilities. LPS-induced NF-κB pathway activation partially averted melatonin’s beneficial effects on ASD mice. Conclusion Melatonin ameliorated ASD-induced CD in mice by modulating the NF-κB pathway and oxidative stress.

Objective Intracranial infection is a serious complication after neurosurgery. However, the early diagnosis of post-neurosurgical intracranial infection (PNICI) remains challenging. The purpose of this study was to compare clinical characteristics and common laboratory indicators in patients with and without intracranial infections after neurosurgery and construct a diagnostic model of PNICI and assess its diagnostic efficacy. Methods A total of 623 patients who underwent neurosurgery from January 2018 to October 2021 were enrolled and divided into a training set and a validation set. SPSS 22.0 software was used to compare the differences in basic information and laboratory examination results between the two groups to screen out valuable indicators. Subsequently, a nomogram for the diagnosis of PNICI was established. Then, the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA) were performed to evaluate the discriminative ability, consistency, and clinical usefulness of the nomogram. Results The diagnostic model of PNICI consisted of seven variables: meningeal irritation, fever, postoperative drainage, cerebrospinal fluid (CSF) white blood cells, CSF chlorine, the CSF/blood glucose ratio, and blood neutrophil percentage. The model achieved an area under the ROC curve of 0.958 in the training set and 0.966 in the validation set. At the optimal cutoff of 0.397, the training set demonstrated 90.4% sensitivity and 90.8% specificity. The calibration curves and DCA curves of the nomogram demonstrated that the model exhibited good goodness of fit and showed a net benefit from its use. Conclusions We developed an easily applicable nomogram using routinely available indicators. This tool enables early risk stratification for PNICI, facilitating timely interventions that may reduce infection-related complications. However, multicenter prospective validation data are required to further confirm the clinical utility.

Objectives Rapamycin is well-known for its protection in neurodegenerative disorders, and mitochondrial dysfunction-related diseases. However, the mechanisms Rapamycin influences mitophagy in juvenile perioperative neurocognitive disorders (PND), remain poorly understood. Methods Female C57BL/6J mice (4–6 weeks) were randomly allocated to four groups: Control (C), Surgery (S), Surgery+Rapamycin (RAPA, Rapamycin 8 mg kg −1 intraperitoneally (i.p.) every other day for 7 days, 24 h before laparotomy), and Surgery+Rapamycin+3-methyladenine (3-MA+RAPA, 3-MA, 2 mg kg −1 i.p. once daily for 7 days, 1 h before Rapamycin injection). Cognitive performance was assessed on post-operative days 1, 3 and 7; hippocampal ROS, ATP, mitochondrial membrane potential, ultrastructure and mitophagy proteins were subsequently evaluated. Results PND occurred in juvenile mice following laparotomy, as evidenced by a decline in Y-maze alternation rate and novel object recognition, increased ROS levels in the hippocampus, and mitochondrial disruptions. Rapamycin protected PND by enhancing mitophagy in hippocampal neurons, reducing ROS accumulation, and preventing mitochondrial damage. Nevertheless, Rapamycin’s neuroprotective effects were abolished by 3-MA administered. Conclusions Rapamycin protects against juvenile PND by stimulating neuronal mitophagy. It offers new insights for pediatrics, but more clinical trials are needed.

Intervertebral disc degeneration (IDD) is a frequent chronic orthopaedic disorder. We investigated the mechanism of miR-376a-5p alleviating IDD through targeting tumor necrosis factor receptor-related factor 6 (TRAF6) to regulate the nuclear factor kappa B (NF-κB) pathway. An in vitro IDD model was established and treated with miR-376a-5p mimic, oe-TRAF6, and the NF-κB inhibitor (BAY 11–7,082). Levels of miR-376a-5p and TRAF6 mRNA, TRAF6, nucleus-p65, cytoplasm-p65 and p-p65, and inflammatory factors TNF-α, IL-1β and IL-6 were determined by RT-qPCR, Western blot, and ELISA. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry assays. The potential binding sites between miR-376a-5p and TRAF6 were predicted and verified by TargetScan database and dual-luciferase assay. LPS-induced NP cells exhibited reduced miR-376a-5p expression, up-regulated TRAF6 expression, weakened cell viability, increased apoptosis, and elevated TNF-α, IL-1β, and IL-6 levels. Overexpression of miR-376a-5p suppressed LPS-induced apoptosis and inflammatory responses and reduced nuclear translocation of p65 protein levels. There were target binding sites between miR-376a-5p and TRAF6. Overexpression of TRAF6 partially reversed the inhibitory roles of miR-376a-5p. Taken together, our study found that miR-376a-5p suppressed LPS-induced apoptosis and inflammatory response in NP cells by targeting the TRAF6/NF-κB pathway, potentially providing a new therapeutic target for IDD treatment.

Objectives Trigonelline (TRIG) is a neuroprotective agent against various nervous system diseases, including ischemic stroke (IS). Microglia-derived exosomes are crucial mediators in modulating IS damage. Herein, this study intended to investigate the protective mechanism of TRIG in IS by targeting microglia-secreted exosomes. Methods IS model in vitro was induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in SK-N-SH cells. Exosomes were extracted from TRIG-treated microglia HMC3 cells, and identified by morphology, particle size, and biomarker expression. Cell viability and cytotoxicity were examined using cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) assay. Enzyme-linked immunosorbent assay (ELISA) and TUNEL assay were performed for assessing inflammation and apoptosis, respectively. The protein expression was tested by Western blotting. Target binding was confirmed by molecular docking and dynamics simulation. Results TRIG-treated HMC3 cells protected SK-N-SH cells from OGD/R-induced viability inhibition, cytotoxicity, inflammation, and apoptosis. Bilayer membrane structures, diameter size of 120 nm, and expressed exosomal markers were observed in exosomes extracted from TRIG-treated HMC3 cells. Exosomes from TRIG-treated HMC3 cells alleviated OGD/R-induced SK-N-SH cell damage via repressing autophagy. Eukaryotic translation initiation factor 5A (EIF5A) was screened as a target of TRIG associated with exosomes, then molecular docking and dynamic simulation indicated the good binding between TRIG and EIF5A. TRIG-treated HMC3 exosomes suppressed OGD/R-induced IS injury by leading to autophagy inhibition through EIF5A. Conclusions This study disclosed the role of TRIG targeting microglia exosomes against IS by regulating EIF5A to affect neuronal autophagy, providing further support for the therapeutic potential of TRIG and its molecular mechanism in IS.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by neuroinflammation and progressive neurodegeneration. Growing evidence suggests that dietary interventions may influence MS progression and symptom management by modulating inflammation, oxidative stress, and gut microbiota composition. This narrative review examines the effects of the Mediterranean, plant-based, ketogenic, Wahls, Swank, intermittent fasting, and gluten-free diets, alongside key nutrients such as omega-3 fatty acids, vitamin D, polyphenols, and antioxidants. Among these, Mediterranean and plant-based diets have shown the most consistent benefits, including reductions in fatigue, improved quality of life, and modulation of inflammatory markers. The Wahls and Swank diets show promise but are primarily supported by studies from their respective research groups, raising concerns about long-term adherence and nutritional adequacy. The ketogenic diet and intermittent fasting have yielded mixed findings, with some studies suggesting benefits for fatigue and neuroprotection, while others highlight potential metabolic risks. The gluten-free diet and omega-3 supplementation lack robust evidence, with inconsistent findings across studies. Additionally, ultra-processed foods and diets high in saturated fats have been associated with increased inflammation and greater MS severity. Despite promising findings, limitations such as small sample sizes, short follow-up durations, and study design inconsistencies prevent definitive conclusions. Future research should prioritize large-scale, long-term randomized controlled trials to establish the efficacy, safety, and sustainability of dietary interventions in MS management. Mechanistic studies and standardized dietary protocols are also needed to better understand the role of diet in MS progression and symptom control.

Prosociality is a behavior characterized by actions performed for the benefit or well-being of others. Recent studies have corroborated parallels in brain activation patterns between rodents and humans during prosocial behaviors. These findings have the potential to advance our understanding of social impairments observed in neurodevelopmental disorders, brain injuries, neurological conditions, and mental health disorders. However, a consensus regarding prosocial paradigms in rodents remains scattered. This conceptual framework aims to (1) reframe prosociality as a set of complex behaviors emerging in response to environmental determinants that cannot be reduced to a single set of data; (2) highlight important methodological considerations, mediating variables, and behavioral analyses that influence prosocial behaviors; and (3) present a decision tree as a dynamic element within this conceptual framework to offer guidance to researchers. The conceptual framework and decision tree are concise and straightforward, providing a robust foundation for the ongoing utilization of current models and the creation of novel paradigms. The integration of this conceptual framework into research practices will contribute to the advancement of knowledge in the field of rodent prosociality and foster greater confidence in the validity and reproducibility of study findings.

Parkinson’s disease (PD) is increasingly understood as a neurodegenerative condition whose pathology extends beyond the direct and indirect basal ganglia pathways. Clinically, patients are all too painfully aware of dysfunction not only of motor circuits but also of somatosensory, autonomic, cognitive, and emotional systems. Functional neuroimaging studies have begun to document a functional reorganization in the PD brain across a wide number of networks. In particular, the cerebellar-thalamocortical, as well as the fronto-striatal circuit, have been shown to undergo functional reorganization. In this narrative review, citing preclinical as well as clinical neuroimaging studies, our objective is to highlight trends and discuss the relevance of cerebral adaptive changes. It remains clear that not all changes contribute to the normalization of functions. Parsing differences between functional “compensation,” “silencing,” or “maladaptation” in neural circuits is important. A necessary next step in neurorehabilitation is the question of whether compensatory cerebral changes can be enhanced. In this regard, physical exercise remains of interest, given that in patients, exercise may allow some degree of symptom improvement and possibly slow the course of the disease. Future interventions may wish to integrate neuroimaging findings as potential targets to support neuroplastic changes.

Episodic memory refers to the recall of memories concerned with unique, personal past experiences. It has been differentiated from semantic or rule learning that may be associatively learned. Episodic memory has the quality of mentally traveling back in time to recover a memory. Episodic memory is believed to be related to language and consciousness, and for this reason, has been thought to be unique to humans. Having episodic memory generally allows one to describe what happened, where it happened, and when it happened. For some time, research has focused on these three properties, and research with animals indicates that several species do have the capacity to behaviorally report the what, where, and when of an event. But such evidence is not sufficient to conclude that animals have episodic memory. Instead, to better distinguish episodic memory from semantic or rule learning, an organism should be able to respond appropriately to an unexpected question about an event that was incidentally rather than explicitly encoded. Using this criterion, there is growing evidence that several species do have such an ability. Furthermore, it is proposed that episodic memory serves to enable future planning, and animals show some evidence for that as well.

Objectives Episodic memory is typically declining in older age but some Superagers have high performance levels. A superager level of performance may be preceded by different trajectories. The purpose of this study was to use longitudinal data to assign Superagers to stable or declining trajectories and then consider variation in memory trajectories in analyses of predictors of Superaging. Methods In the longitudinal Betula study we identified 139 Superagers (Mean age=79 years) with as good or higher episodic memory as the average of 300 50–60 years old individuals. Episodic-memory trajectories of 125 Superagers were defined from up to 25 years of longitudinal data. The Betula database provided information on possible predictors of Superaging, including education, cognition, polygenic scores, health, lifestyle, and structural brain integrity. Results The majority of Superagers were on stable trajectories from initially high to average levels, but some were on declining trajectories from high levels. Similar longitudinal profiles were seen on a word-fluency task. Analyses of predictors of Superaging revealed that education and a polygenic score for cognition were related to initial memory level, and that a polygenic score for dementia was related to rate of change. Most but not all superagers with high-stable memory had favorable education and polygenic predictor scores, suggesting alternative pathways to Superaging. Longitudinal imaging data revealed less atrophy in entorhinal cortex and hippocampus for Superagers. Conclusion A superager performance level can reflect well-maintained memory or decline from high initial levels, with distinct factors explaining variability in initial level or stability over time. Medial-temporal lobe brain maintenance characterizes episodic-memory Superagers.

Memory disorders belong to the most common concomitants of brain damage, but can be found as well in cases without directly measurable brain damage. These then belong in the category of psychiatric diseases. One of them, with frequently long-lasting memory deficits in the episodic-autobiographical domain, is named functional amnesia . Functional amnesia is characterized by retrograde amnesia, implying that usually all the personal past is [consciously] inaccessible to the affected individual. Based on Tulving’s definition of episodic-autobiographical memory we describe the condition of functional amnesia, pointing to closely related conditions such as hysterical or psychogenic or dissociative amnesia, medically unexplained amnesia, repression and suppression, and mnestic block syndrome. The fugue syndrome is considered to be a more special and rare form of functional amnesia. Common symptoms such as belle indifference , personal insecurity, and changes in consciousness are highlighted, as well as precipitants and concomitants of functional amnesia. It is explained, why functional amnesia can be regarded to be a ‘helpful amnesia’. By describing five special cases, we point to the spectrum of functional amnesic states.