International Journal of Neuroscience最新文献

Background: There is a lack of actual and comprehensive data on the detection rate of neuronal surface antibodies in patients with unexplained epilepsy in China. Thus, we attempted to analyze the differences in clinical manifestations, cerebrospinal fluid (CSF) characteristics, seizure types and other aspects of antibody-positive and negative patients, to identify suspected antibody-positive epilepsy patients.

Methods: In total, 137 inpatients with unexplained epilepsy were consecutively included, and neuronal surface antibodies (NSAbs) were detected by serological and/or CSF evaluations. The clinical features and seizure characteristics were analyzed between the NSAb-positive and negative patients. In addition, patients were divided into four groups based on CSF and blood antibody titers. CSF cell count and protein content were analyzed in relation to antibody titers.

Results: There were 45 (32.8%) patients tested positive for antibodies. Multivariate analyses revealed that age, mental status changes or memory deterioration, CSF protein, CSF cell count, treatment, days of hospitalization, outcome, duration of symptoms before hospitalization, status epilepticus, and number of antiepileptic drugs were significantly associated with the NSAb-positive group and changes in inflammatory indicators in routine CSF analysis were associated with antibody titers.

Conclusions: A relatively high proportion of patients with unexplained epilepsy have positive NSAbs. Patients with the above clinical characteristics need to be highly suspected of NSAbs positivity and should be tested for antibodies in time to assist treatment. The decrease of CSF cell count and protein content has suggestive value for the decrease of antibody titer, which should be evaluated in the follow-up.

Aim: Postoperative cognitive dysfunction (POCD) is a common postoperative complication, especially in elderly patients. It extends hospital stay, increases the mortality rate and are heavy burdens to the family and society. Accumulating research has indicated that overactivation of pyrin domain-containing protein 3 (NLRP3) inflammasomes is related to POCD andplays a critical role in activating pro-inflammatory cytokines. According to existing studies, indoleamine 2,3-dioxygenase (IDO) is potently up-regulated by inflammatory factors, tryptophan in brain is mainly catalyzed by IDO to kynurenine (KYN), KYN metabolism may contribute to the development of depressive disorder and memory deficits. Hence, this study elucidated whether IDO-Kynurenine pathway mediates NLRP3 inflammasome activation-induced postoperative cognitive impairment in aged mice.

Material and methods: POCD model was established in aged C57BL/6J mice by exploratory laparotomy under isoflurane anesthesia. Learning and memory were determined using Morris water maze.

Results: The data showed that IDO and kynurenine aminotransferase-II (KAT-II) mRNA in hippocampus was up-regulated, and NLRP3, caspase recruitment domain (ASC), interleukin-1b (IL-1b) and IDO overexpressed, KYN levels increased after anesthesia and surgery. NLRP3 inflammasome inhibitor (MCC950) reversed NLRP3, ASC, IL-1b and IDO overexpression, and the elevation of KYN levels. To clarify the role of IDO-Kynurenine pathway in postoperative cognitive impairment, IDO inhibitor (1-methyl-Ltryptophan 1-MT) reduced the elevation of KYN and kynurenic acid (KYNA) levels, reduction of tryptophan (TRP), as well as improved learning and memory abilities. Finally, KAT-II inhibitor (PF-04859989) reduced brain KYNA levels and restored the cognitive impairment.

Conclusion: These results reveal that IDO-Kynurenine pathway mediates NLRP3 inflammasome activation-induced postoperative cognitive impairment.

Background: Failure of delayed neurological improvement (fDNI) following successful recanalization is a prevalent clinical phenomenon in patients who have experienced acute ischemic stroke (AIS). An investigation into the potential link between markers of systemic inflammation such as platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index known as SII, and the occurrence of fDNI in patients received successful reperfusion was conducted.

Methods: The study included patients diagnosed with AIS who underwent thrombectomy and experienced fDNI, as observed in a prospective study conducted from January 2017 to April 2020. In order to identify predictors of fDNI, we performed multivariable logistic regression and receiver operating characteristic (ROC) curve.

Results: Eighty-four patients (23.86%) without early neurological improvement (ENI) experienced DNI, and 268 (76.14%) patients did not show DNI. After adjustment for potential confounders, NLR (adjust OR, 2.131; 95%CI, 1.066-4.259; p = 0.032) and SII (adjust OR, 1.065; 95%CI, 1.001-1.132, p = 0.045) exhibited independent reationship with fDNI independently in multivariate analysis. The areas under AUC of multivariable NLR and SII mode were 0.862 and 0.861, respectively.

Conclusions: The immune-inflammatory biomarkers, including NLR and SII, exhibited associations with DNI in patients without ENI. Further investigations are warranted to elucidate the underlying mechanisms.

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has recently reported to prevent the depression in chronic animal model. The present study aimed to explore the antidepressant potential of empagliflozin using a neuroinflammation-mediated depression involving the olfactory bulbectomy (OBX) model in diabetic rats. A low dose of streptozotocin was injected to induce diabetes in all group of animals. Following the confirmation of hyperglycemia, OBX surgery was performed. Post-surgery, the drug treatments were administered orally for 14 consecutive days. The study evaluated the effects of daily oral administration of empagliflozin at doses of 5 and 10 mg/kg, alongside metformin (200 mg/kg) and clomipramine (50 mg/kg), on OBX-induced behavioral depression in rats. Separate sham and vehicle control groups were also maintained. Behavioral parameters in open field, forced swim test, elevated plus maze and splash test were recorded on 28^th day. Results showed that empagliflozin, at the higher dose, significantly enhanced behavioral outcomes, evidenced by increased distance travelled, greater open arm entries, and reduced immobility, alongside a notable reduction in grooming time. Moreover, empagliflozin significantly restored the antioxidants level specifically Glutathione (GSH) and Catalase (CAT) in OBX insulted rat brain and decreased Lipid peroxidase (LPO). Notably, molecular docking study demonstrated a good binding affinity of empagliflozin for Brain-Derived Neurotrophic Factor (BDNF), suggesting that its antidepressant effects may be mediated through the modulation of the BDNF pathway. These findings support the potential therapeutic application of empagliflozin for depression, particularly in cases associated with neuroinflammation and oxidative stress.

Purpose/aim of the study: The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment.

Materials and methods: MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks.

Results: Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks.

Conclusions: These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.

Brainstem cavernous malformations are benign subset of cerebral cavernous malformations, which need a special intervention owing to being vital and complex. The diffusion tensor imaging technique, a well-recognized neuroimaging tool, can visualize the white matter tracts and their surroundings and provide promising surgical outcomes. This systematic review and meta-analysis evaluated the effect of preoperative diffusion tensor imaging in patients undergoing surgical resection of brainstem cavernous malformations. Five databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, were searched using a comprehensive search strategy to find any article matching our inclusion criteria. We used Comprehensive Meta-Analysis (CMA) software to analyze the collected data, get the evidence, and report the results as event rate (ER), with their 95% confidence interval (CI). Twenty-eight studies involving 467 patients matched our criteria and 19 studies entered the analysis. Our analysis showed that, in patients undergoing surgical resection of brainstem cavernous malformations assisted by preoperative diffusion tensor imaging, 82.21% achieved total resection. About 12.4% of patients achieved partial resection, 65.65% improved, 8.07% worsened, 25.04% showed no change, 3.59% experienced postoperative re-bleeding, and 0.87% died. The utilization of preoperative diffusion tensor imaging significantly increased the proportion of improved patients and decreased the proportion of worsened patients. However, further controlled research is needed to draw a definite conclusion about the usefulness of its role.

Background and objectives: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study.

Methods: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded.

Results: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants.

Conclusion: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors.

Objectives: Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant neurodegenerative disease, which is characterized by iron accumulation in the basal ganglia. BPAN is associated with pathogenic variation in WDR45, which has been reported almost exclusively in females most probably due to male lethality in the hemizygous state.

Methods: Whole exome sequencing (WES) and targeted deep sequencing were performed for a male with a clinical diagnosis of BPAN at the age of 37.

Results: The novel frameshift variant in WDR45 detected by WES was further analyzed with targeted resequencing to detect a mosaic variant with a level of 85.5% in the blood sample of the proband.

Discussion: Although the main role of WDR45 remains elusive, recent studies show that WDR45 may contribute to neurodegeneration through defects in autophagy, iron storage and ferritin metabolism, mitochondria organization, and endoplasmic reticulum homeostasis. The extend of spatiotemporal haploinsufficiency of WDR45 frameshifting variants caused by mosaicism in males may lead to variable clinical severity, which may be hard to elaborate clinically. Promising genetic analysis strategies using targeted deep sequencing may help determine the clinical outcome of somatic mosaicism in neurological disorders including BPAN. Additionally, we suggest that deep sequencing should be conducted in cerebrospinal fluid samples to provide more reliable results in terms of reflecting the mosaicism level in the brain for future studies.

Aim: This paper aimed to answer how psychometric methods based on neurotypical populations can serve as valid instruments in the assessment and diagnosis of intellectual disability in individuals with atypical development. The genetic, structural, and functional features of CHARGE make it uniquely suited to address this question.

Method: A Norwegian population of individuals with CHARGE (N = 35) underwent assessment procedures according to DSM-5 guidelines for the evaluation of an intellectual disability diagnosis. Results from cognitive testing (Wechsler Intelligence Scales) and parental evaluation of adaptive skills (Vineland Adaptive Behavioral Scale) were obtained and compared to their respective norm samples to explore any methodological inconsistencies.

Result: Significant differences emerged between the participants and the norm samples. Global cognition obtained from Wechsler revealed a bimodal distribution, suggesting a two-group sample, with the youngest children forming their own subgroup. Comparisons of the different age-groups' performances demonstrated the lowest results among the preschoolers while the adults scored the highest. The global adaptive behavior score turned out significantly lower than the performance-based scores, thereby deflating the overall estimate of global intellectual abilities.

Conclusion: For individuals with CHARGE, the effect of the atypicality seemed most apparent during early childhood, stabilizing and subsiding towards adulthood. The test results' interpretability was weakest for the preschoolers progressively increasing until peaking in adulthood, emphasizing the importance of delaying the assessment and diagnosis of intellectual disability. Because of several validity issues connected to the observation-based measure, complementary testing should precede clinical evaluations when possible in the diagnostics of individuals with CHARGE.