Neurological Research最新文献

Objectives: Exposure to aluminum (Al) has been shown to be strongly associated with the pathogenesis of Alzheimer's disease (AD). Recent evidence indicates that the toxicity of Al nanoparticle (Al-NP) is far greater than Al itself due to its particle size. Epidemiological studies suggest that curcumin lower the prevalence of AD. MAPKs (ERK, p38 and JNK) were suggested to be involved in AD pathology and memory impairment. The present study aimed to evaluate if curcumin has the ability to protect against behavioral deficits induced by subcutaneously administered Al-NP in mice. Furthermore, the levels of phosphorylated and total hippocampal MAPKs were assessed using western blottechnique.

Methods: Al-NP (10 mg/kg/s.c.) was administered to adult male NMRI mice for 10 days with or without curcumin in doses of 2.5 or 25 mg/kg/oral gavage). Memory was assessed using passive avoidance apparatus and anxiety-like behavior was evaluated using elevated plus maze. Following the behavioral tasks, western blot analysis was performed on the hippocampal tissues to detect the levels of phosphorylated and total MAPKs.

Results: The results revealed that Al-NP deteriorated memory with no significant effect on anxiety-like behaviors. Additionally, it activated hippocampal p38 signaling pathway with no effect on ERK and JNK. Curcumin treatment at the dose of 25 mg/kg restored memory and p38 activation.

Discussion: This study suggests that subcutaneous Al-NP administration impairs memory and hippocampal p38 signaling with no effect on ERK and JNK. Co-administration of curcumin restored Al-NP induced memory impairment and hippocampal p38 phosphorylation.

Objectives: Since neurogenic inflammation and hemoconcentration have a prominent role in the pathophysiology of migraine, evaluation of hemogram parameters and indices showing inflammation can yield important information. In this study, we have investigated blood cell counts and ratios, systemic inflammation index (SII), systemic inflammation response index (SIRI) and red cell index (RCI) in the painless periods between pain attacks in patients with episodic migraine without aura.

Methods: Hemogram data of both 309 patients diagnosed with migraine without aura related to pain-free periods and 199 healthy individuals were retrospectively retrieved from hospital records. Data related to erythrocyte, leukocyte, lymphocyte, platelet, monocyte, eosinophil counts; hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width (RDW), mean platelet volume (MPV), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio (MLR), and neutrophil/monocyte ratio, SII, SIRI and RCI values were scanned to reveal intergroup differences in terms of these parameters.

Results: A comparison of laboratory parameters revealed that certain indices differed significantly between the migraine and control groups. MLR (p = 0.005) and RDW (p < 0.001) values were significantly lower, while platelet (p = 0.016), MPV (p < 0.001) and hematocrit (p = 0.014) were significantly higher in the migraine patient group compared to the control group. There was no significant difference between the two groups regarding other parameters.

Discussion: Higher hematocrit, platelet, mean platelet volume and lower monocyte/lymphocyte ratio values in this study support that hemoconcentration and chronic inflammation persist even in the absence of pain attacks in migraine patients without aura.

Objectives: Intracranial aneurysms (IA), often remain asymptomatic until they get ruptured, invariably leads to subarachnoid hemorrhage (SAH), and is influenced by both genetic and environmental factors. Recent studies indicated inflammation as a key player in IA development. This study delves into genetic variations within inflammatory pathways, focusing on TLR4-mediated cytokine release as potential IA biomarkers.

Methods: Eighty IA patients and eighty healthy controls from North India participated, and demographic and clinical data were analyzed, including gender-stratified comparisons of TLR4 Asp299Gly genotype and TLR4 expression. Histological and molecular analyses of blood and brain tissue were done using SEM imaging, qPCR, and western blot.

Results: Our result revealed elevated TLR4 expression in IA patients, with SEM imaging indicating intracerebral damage. TLR4 Asp299Gly heterozygote genotype was less prevalent in IA patients, suggesting a protective effect against IA development. Moreover, TNF-α levels were significantly higher in IA patients, indicating an inflammatory response. Further, TNF-α expression was downregulated in heterozygous patients, suggesting TLR4 Asp299Gly gene polymorphism affects the activation of TNF-α expression. Gender-based analysis between control and aneurysm cases showed a decrease in TLR4 Asp299Gly heterozygote genotype with heightened TLR4 expression and neurological deficits in IA female patients compared to males.

Conclusions: This study highlights the association between TLR4 Asp299Gly genotype and IA susceptibility in North Indian populations, linking increased TLR4 expression to IA pathogenesis. Gender-specific disparities in TLR4 genotype and expression underscore the need for personalized treatment strategies, with TLR4 signaling modulation emerging as a promising therapeutic avenue warranting further investigation.

Objectives: Due to the complex and unclear pathogenesis of neuropathic pain, there is a lack of effective therapeutic strategy. miR-363-5p was considered of great potential in mediating the development of neuropathic pain, which has not been confirmed with direct evidence. This study evaluated the role of miR-363-5p in neuropathic pain with animal and cell models, aiming to reveal the potential of miR-363-5p in target therapy of neuropathic pain.

Methods: Chronic constriction injury (CCI) rat models were established as the neuropathic pain model. The expression of miR-363-5p and its target was evaluated by PCR. The painology behaviors were evaluated to assess the function of miR-363-5p. Schwann cells were induced with LPS mimicking cell injury during neuropathic pain. Inflammation and cell growth were estimated by ELISA and CCK8 assays.

Results: Significant downregulation of miR-363-5p and upregulation of SERPING1 were observed in CCI rats. miR-363-5p negatively regulated SERPING1 in CCI rats and LPS-induced Schwann cells. Overexpressing miR-363-5p could improve pain threshold and alleviate inflammation in CCI rats. It also a ttenuated LPS-induced inflammation and reduced proliferation in Schwann cells. The overexpression of SERPING1 could reverse the protective effect of miR-363-5p on CCI rats and LPS-induced Schwann cell injury.

Conclusion: miR-363-5p protected from neuropathic pain via alleviating Schwann cell injury by negatively modulating SERPING1.

Background: Galcanezumab is a monoclonal antibody targeting the CGRP pathway and represents the latest disease-specific and mechanism-based therapeutic option for cluster headache (CH).

Objective: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of galcanezumab for CH.

Methods: We searched PubMed, Embase, and Cochrane Library for studies implementing galcanezumab for episodic and chronic CH. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Reporting Guidelines for Meta-analyses of Observational Studies (MOOSE) guidelines. The primary outcome was efficacy, defined by a reduction from the baseline of at least 50% in the weekly frequency of CH attacks and the Patient Global Impression of Improvement scale (PGI-I). Secondary outcomes included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Results: A total of 504 patients were included from 6 studies, of which 2 were RCTs. The follow-up period ranged from 3 weeks to 15 months. The mean age was 44.4 ± 10.2 years, with 24.4% female patients. Overall efficacy was 76.0% (95% CI 0.67-0.85), TEAEs were observed in 48.0% of patients (95% CI 0.25-0.72), and the most common were nasopharyngitis, local injection pain, and local injection swelling. TEAEs were, however, considerably higher within the 300 mg dose group compared with the 240 mg dose group, 80.0% (95% CI 0.65-0.87) versus 28.0% (95% CI 0.12-0.47), respectively.

Conclusion: This meta-analysis suggests that galcanezumab is effective in reducing the number of CH attacks and can be considered a safe medication.

Objective: This study aims to investigate Auditory Evoked Brainstem Responses (ABR) and Distortion Product Otoacoustic Emission (DPOAE) suppression in migraine patients with and without phonophobia.

Methods: Thirty-two migraine patients with normal hearing and 30 healthy individuals were included in the study. Migraine characteristics and phonophobia status of migraine patients were noted. The patients were divided into two groups according to their phonophobia status. All participants underwent ABR, DPOAE and DPOAE suppression.

Results: Migraine patients had less DPOAE suppression (1481 and 2222 hz) and shorter ABR wave latencies compared to the control group (p < 0.05). Twelve (37.5%) of the migraine patients did not have phonophobia, and 20 (62.5%) had phonophobia. Phonophobia was not found to affect DPOAE suppression (p > 0.05). However, ABR wave I and V latencies in migraine patients with phonophobia were shorter than in healthy individuals (p < 0.05).

Conclusion: There are changes in the auditory evoked brainstem responses and medial olivocochlear efferent system of migraine patients. While phonophobia in migraine patients does not affect the medial olivocochlear efferent system, it may affect auditory evoked brainstem responses.

Objectives: To explore a novel model of mobile stroke units (MSUs) integrated with rural emergency medical stations for pre-hospital care of stroke patients in remote areas.

Methods: We used MSUs + Ambulance mode, where both the MSUs and conventional ambulances are sent to the patient's location. The conventional ambulance coordinates with the MSUs to choose the fastest route to meet and transfer the patient at the point along the way. We collected data from 149 patients from March 2022 to April 2023, including National Institutes of Health Stroke Scale (NIHSS) scores (on admission, 24 hours, day 7), 90-day modified Rankin Scale (mRS) scores, and other clinical variables. We performed propensity score matching (PSM) to balance the potential confounding variables between groups.

Results: We found that the MSUs + Ambulance mode (OR = 12.507, 95% confidence interval [CI] [3.633, 43.061], p < 0.001) and admission NIHSS score (OR = 0.583, 95% CI [0.493, 0.690], p < 0.001) were independent prognostic risk factors for stroke patients. The MSUs + Ambulance mode reduced NIHSS scores 7 days prior to admission (OR = 0.679, 95% CI [0.563, 0.819], p < 0.001). After PSM, patients who received MSUs + Ambulance mode had a better prognosis (χ² = 9.573, p = 0.004), as well as a lower mRS score at 90 days (Z = -3.371, p = 0.001).

Conclusions: MSUs integrated with rural emergency medical stations show the feasibility and potential benefits of pre-hospital intravenous thrombolysis for stroke patients in geographically distant regions.

Purpose: The effectiveness of reactive responses to a sudden loss of balance is a critical factor that determines whether a fall will occur. We examined the strategies and kinematics associated with successful and unsuccessful balance recovery following lateral loss of balance in people with stroke (PwS).

Methods: Eleven PwS were included in the analysis. They were exposed to unannounced right and left horizontal surface translations and demonstrated both successful and unsuccessful balance responses at the same perturbation magnitude. Reactive step strategies and kinematics were investigated comparatively in successful and unsuccessful recovery tests.

Results: The crossover strategy was used in most of the unsuccessful tests (7/11) while the unloaded-leg side-step in the successful tests (6/11). There were no significant differences in the reactive step initiation time in unsuccessful vs. successful tests. However, the step execution time, step length and center of mass displacement were significantly higher during the first recovery step in unsuccessful tests.

Conclusions: PwS have difficulties in controlling and decelerating the moving center of mass following a lateral loss of balance. The increased step time and step length of the first reactive step in unsuccessful vs. successful tests suggest the crossover step strategy may be ineffective for PwS.

Objectives: The purpose of this study was to evaluate the relationship between changes in skeletal muscle mass and improvements in swallowing function in stroke patients with dysphagia during rehabilitation.

Methods: The study included 145 patients with a stroke or dysphagia. The two groups were divided into two groups: those with improved skeletal muscle mass index (SMI) at discharge and those without. Clinical data, including SMI, and Mann Assessment of Swallowing Ability (MASA), were collected from the database.

Results: The increase in MASA was significantly higher in the group with increased SMI than in the group with no increase in SMI. In the multivariate analysis, the duration of rehabilitation and the group with increased SMI were associated with increased MASA.

Conclusion: SMI gain and the duration of rehabilitation per day were associated with improved swallowing function in patients with stroke.

Background: Glioblastoma (GBM) is a brain tumor with poor prognosis. Dexmedetomidine (Dex) regulates the biological behaviors of tumor cells to accelerate or decelerate cancer progression.

Objective: We investigated the effects of Dex on the migration, invasion, and glycolysis in GBM.

Methods: The concentration of Dex was determined using the cell counting kit-8 assay. The impacts of Dex on biological behaviors of GBM cells were assessed using Transwell assay, XF96 extracellular flux analysis, and western blot. The expression of c-Myc was examined using reverse transcription-quantitative polymerase chain reaction. The lactylation or stability of c-Myc was measured by western blot after immunoprecipitation or cycloheximide treatment.

Results: We found that Dex (200 nM) inhibited GBM cell viability, migration, invasion, and glycolysis. C-Myc was highly expressed in GBM cells and was decreased by Dex treatment. Moreover, Dex suppressed lactylated c-Myc levels via suppressing glycolysis, thereby reducing the protein stability of c-Myc. Sodium lactate treatment abrogated the effects of Dex on the biological behaviors of GBM cells.

Conclusion: Dex suppressed the migration, invasion, and glycolysis of GBM cells via inhibiting lactylation of c-Myc and suppressing the c-Myc stability, suggesting that Dex may be a novel therapeutic drug for GBM treatment.