Neurological Research最新文献

Background: Sporadic global cognitive decline is on the rise, and current drugs exhibit limited efficacy. Propionate, an SCFAs of the human microbiome, exhibits robust neuroprotective effects.

Methods: We used CCK8 to evaluate neuronal proliferation, DCFH-DA fluorescence probe to quantify ROS production, ELISA to detect IL-1β and IL-6 release, MitoTracker to assess mitochondrial membrane potential, real-time quantitative PCR, and western blotting to analyze DRP1 and anti-Mfn2 protein expression. We also established an in vitro blood-brain barrier model and AD mouse model.

Results: Propionate normalized the mitochondrial membrane potential in glutamate-treated HT22 cells, reversed growth suppression, ROS accumulation, and elevated IL-1 and IL-6 release. Propionate also decreases Drp1 expression and elevates Mfn2 expression via GRP41 receptor binding. In vitro blood-brain barrier models illustrated the potential of propionate to ameliorate glutamate-induced blood-brain barrier damage. In vivo, propionate notably improved the learning and memory capabilities of AD mice and mitigated AD-induced mitochondrial defects.

Conclusion: Supplementation with propionate provides neuroprotection against neurodegenerative diseases. Propionate supplementation may provide a novel strategy for early intervention of neurological disorders.

Background: Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder. There is currently no promising cure for AD; the available treatments can only alleviate the symptoms.

Objectives: The Benzofuran-Enaminone derivative '(E)-1-(benzofuran-2-yl)-3-((2-hydroxyphenyl)amino)prop-2-en-1-one (5)' was synthesized as a potential anti-AD candidate in Aluminum chloride (AlCl₃)-induced AD in rats.

Methods: In vivo and in vitro acute and chronic studies were conducted to examine the potential toxicity, as well as the antioxidant and anti-acetylcholinesterase (AChE) activities of compound 5. Then, rats were divided into four groups: (1) negative control; (2) AD-induced rats; (3) AD-induced rats treated with compound 5; and (4) AD-induced rats treated with Donepezil. Behavioral, biochemical, and molecular investigations were conducted. The expression of insulin 1 gene, apoptotic genes, and the AD-related genes were estimated.

Results: The selected dose of compound 5 (10 mg/kg) was based on an acute toxicity test, then it was applied for a chronic study for 1 month; no toxicological features were stimulated. In vitro, compound 5 demonstrated antioxidant and anti-AChE activities. The expression of apoptotic genes (Bcl-2, Bax, and Caspase-3), AD-related genes (Amyloid precursor protein (APP) and Tau), and the insulin 1 gene were altered in AD-induced rats versus control rats. Treatment of AD rats with compound 5 counteracted the AlCl₃-induced neurotoxicity.

Conclusion: This study could be regarded as an initial step in drug discovery for testing this new chemical entity as a potent anti-AD therapeutic agent.

Objective: Currently available treatment options for multiple sclerosis (MS) have limited efficacy and/or safety concerns. Various mesenchymal stem cells and hematopoietic stem cells have been evaluated in recent clinical trials. The present meta-analysis was conducted to assess the safety and efficacy of stem cell therapy in multiple sclerosis.

Methods: PubMed/MEDLINE, EMBASE, Cochrane Database, Scopus, and clinical trial registries were searched, and 11 RCTs were included. Quality assessment was performed using the risk-of-bias assessment 2 tool, and the random-effects model was used to estimate the effect size. Subgroup analysis, sensitivity analysis, and meta-regression were performed as applicable. PRISMA reporting guidelines were followed for reporting.

Results: A total data of 691 patients from 11 RCTs were included, and it showed that there was a greater change in EDSS score from baseline in the stem cell therapy arm as compared to the control arm (MD:-0.35; 95%CI: -0.79 to 0.08; p = 0.104), but was not significant statistically. The change in number of T2 lesions was also not statistically significant between the groups (MD:-0.75; 95%CI: -4.16 to 2.66; p = 0.619). Number of patients with at least one TEAE were comparable between the groups (OR:0.99; 95%CI: 0.61 to 1.62; p = 0.977).

Conclusion: Stem cell therapy is safe; however, it is no better than control (mostly placebo, mitoxantrone and conventional disease-modifying therapy) in the treatment of MS. Well-designed, adequately powered randomized controlled trials focusing on standardized stem cell types, routes, and dosing are essential to clarify their therapeutic role in multiple sclerosis.

Prospero registration number: CRD42023457808.

Background: Carotid artery stenosis (CAS) reduces cerebral blood flow and is frequently associated with cognitive impairment and reduced quality of life (QoL), particularly in severe CAS. Although carotid revascularization (stenting or endarterectomy) can improve blood flow and potentially enhance cognitive function and QoL, the impact of CAS before revascularization remains unclear.

Objective: This review aimed to synthesize the literature exploring the relationship between CAS, cognitive impairment, and QoL, focusing on pre-revascularization outcomes.

Method: A comprehensive scoping review was conducted using PubMed, CINAHL, MEDLINE, EMBASE, PsycINFO, EBSCO, and Scopus to identify relevant studies published between 2015 and 2023.

Results: This review identified consistent evidence linking severe CAS (≥70%) to significant cognitive decline, particularly in areas such as memory, attention, and executive function. Although carotid revascularization showed promise in improving cognitive performance, the extent of recovery varied. Studies also highlighted the profound impact of CAS on QoL, with patients frequently experiencing anxiety, depression, and physical limitations. While revascularization procedures were associated with improvements in physical functioning and overall well-being, emotional recovery often delayed.

Conclusion: CAS substantially affects both cognitive functioning and QoL, even before revascularization. Although some studies suggested that revascularization may lead to improvements in cerebral perfusion and certain domains of cognitive function, the trajectory of psychosocial and emotional recovery; including depressive symptoms, anxiety, and fear of future cerebrovascular events, demonstrates delayed improvement. These emotional outcomes mediate overall QoL and should be a focus of both clinical assessment and future longitudinal studies. Standardization of cognitive and psychosocial outcome measures is essential.

Background and objective: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, oxidative stress, and mitochondrial dysfunction. Fibroblast growth factor 21 (FGF21) has demonstrated neuroprotective effects, though its role in AD pathogenesis remains unclear. The present study aims to discover neuroprotective effects of FGF21 in AD by examining its influence on energy metabolism and neuronal survival through the PI3K/Akt signaling pathways.

Methods: In vivo experiments were performed using 5×FAD transgenic mice, while in vitro assays utilized amyloid beta 1-42 (Aβ1-42)-treated SH-SY5Y cells and a co-culture system of primary rat astrocytes with SH-SY5Y cells. To evaluate the effects of FGF21 modulation, we performed both gain- and loss-of-function experiments and assessed outcomes using behavioral testing, histopathological and ultrastructural analyses, oxidative stress and mitochondrial function assays, and Western blotting. The involvement of the PI3K/Akt/mTOR pathway was explored using the PI3K inhibitor LY294002.

Results: Both in vivo and in vitro AD models exhibited reduced FGF21 expression. FGF21 downregulation impaired PI3K/Akt signaling, induced neuronal apoptosis, and disrupted metabolic homeostasis. Loss of FGF21 resulted in cognitive and metabolic dysfunction in AD mice. Conversely, FGF21 overexpression activated PI3K/Akt signaling, suppressed neuronal apoptosis, and restored metabolic functions in AD models.

Conclusion: FGF21 alleviates AD-related cognitive impairment and restores metabolic function by activating the PI3K/Akt pathway.

Objective: To investigate the association between thrombin-activatable fibrinolysis inhibitor (TAFI) genetic polymorphisms and therapeutic efficacy in spontaneous intracerebral hemorrhage (ICH) patients treated with intra-hematoma rt-PA thrombolysis.

Methods: This retrospective exploratory study analyzed 59 ICH patients who underwent intra-hematoma rt-PA thrombolysis. TAFI polymorphism genotyping was performed using PCR-RFLP. Primary outcomes included radiological efficacy, functional outcomes (mRS ≤3), and mortality.

Results: Genetic analysis was completed in 55 patients. Genotype distribution: Ile325Ile 28 (47.5%), Thr325Ile 25 (42.4%), Thr325Thr 2 (3.4%), consistent with Hardy-Weinberg equilibrium (P=0.35). The Ile325Ile group showed a trend toward better functional outcomes compared to Thr325Ile (25.0% vs 8.0%, OR=3.83, P=0.108), but had significantly higher mortality (14.3% vs 0%, P=0.042). Multivariate analysis identified age (OR=0.948, P=0.024) and admission NIHSS score (OR=0.908, P=0.021) as independent predictors of good functional outcomes; TAFI genotype was not retained as an independent predictor (P=0.138).

Conclusions: This exploratory study provides preliminary evidence that TAFI genetic polymorphisms may be associated with differential responses to intra-hematoma rt-PA thrombolysis, with potential genotype-dependent dissociation between radiological and functional outcomes. These findings require validation in larger studies.

Objective: To evaluate remission, recurrence, and complication rates following endoscopic transsphenoidal surgery (ETSS) for Cushing disease (CD) at a Canadian tertiary center, and assess concordance of preoperative cerebral MRI and inferior petrosal sinus sampling (IPSS) with intraoperative adenoma laterality.

Methods: We retrospectively reviewed 92 patients with confirmed CD who underwent ETSS by a single neurosurgeon between August 2007 and May 2025. Outcomes included biochemical remission, recurrence, and complications. We assessed the concordance of preoperative MRI and IPSS with intraoperative tumor localization.

Results: The cohort included 92 patients (mean age 46.6 ± 15.0 years; 77% female) with a median follow-up of 18.3 months (IQR 6.4-44.9). Preoperative MRI identified a microadenoma in 63 cases, macroadenoma in 17, and was negative in 12. Remission was achieved in 76.7% (86.4% early ≤6 months), with 7.9% experiencing recurrence after a median of 13.2 months. Complications included arginine vasopressin deficiency (AVPD) in 43.5% of the cohort (persistent >6 months in 10.2%), hypothyroidism in 14.1%, syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 5.4%, and cerebrospinal fluid (CSF) leak in 3.3%. Intraoperatively, 78.8% of microadenomas were in the posterior adenohypophysis, and 27.4% exhibited multifocal distribution. Concordance of adenoma laterality was 56.5% for MRI and 41.7% for IPSS, with no statistically significant difference.

Conclusion: ETSS achieved high remission with low morbidity in CD. Frequent posterior and multifocal adenomas in the adenohypophysis support systematic pituitary exploration. Localization remains challenging, with limited concordance using MRI and IPSS, highlighting the need for cautious interpretation in surgical planning.

Background: Traumatic brain injury (TBI) triggers secondary neuronal damage via oxidative stress and ferroptosis. This study examines the neuroprotective effect of fibroblast growth factor 21 (FGF21) in TBI and its regulation of the Nrf2/GPX4 signaling pathway.

Methods: TBI was induced in C57BL/6 mice using a controlled cortical impact model. Post-injury, mice received low- or high-dose recombinant FGF21, with or without the Nrf2 inhibitor ML385. Neurological function was evaluated using Garcia scoring and the Morris Water Maze. Oxidative stress, cerebral edema, and iron deposition were measured. In vitro, primary rat cortical neurons were treated with erastin (a ferroptosis inducer) ± FGF21 or ferrostatin-1. Neuronal viability, morphology, and Nrf2/GPX4 expression were analyzed by immunofluorescence, Western blotting, and RT-qPCR.

Results: FGF21 significantly improved neurological outcomes in TBI mice, reduced edema and iron deposition, and attenuated oxidative stress. In vitro, FGF21 preserved neuronal structure and viability under ferroptotic conditions. Mechanistically, it enhanced Nrf2 nuclear translocation and upregulated GPX4. These effects were abolished by Nrf2 inhibition, confirming pathway involvement.

Conclusion: FGF21 protects against TBI-induced secondary injury by suppressing ferroptosis and oxidative stress via Nrf2/GPX4 activation, highlighting its potential as a therapeutic strategy for TBI.