Neurological Research最新文献

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.

Objective: This study aims to investigate the association of clinical characteristics, vascular morphological features, and hemodynamic parameters with rupture risk in anterior communicating artery (ACoA) aneurysms.

Methods: A retrospective analysis was conducted on 293 patients with ACoA aneurysms, categorized into ruptured and unruptured groups. Clinical data, vascular morphological parameters, and hemodynamic variables were compared between groups. Binary logistic regression analysis was used to identify independent predictors of aneurysm rupture.

Results: Statistically significant differences were observed between the ruptured and unruptured groups in terms of sex, smoking status, systolic and diastolic blood pressure at admission, curvature of the affected A1 segment, spatial angle between the affected internal carotid artery and ipsilateral A1 segment, and the curvature length of the A1 segment. Hemodynamic parameters, including wall shear stress (WSS) and the presence of blood flow vortices, were notably elevated in ruptured aneurysms. Binary logistic regression analysis identified the curvature of the affected A1 segment (odds ratio [OR] = 0.001, 95% confidence interval [CI]: 0.000-0.173, p = 0.010), the angle between the affected A1 and A2 segments (OR = 0.963, 95% CI: 0.933-0.994, p = 0.020), and WSS on the affected side (OR = 0.140, 95% CI: 0.072-0.269, p < 0.001) as significant independent indicators of rupture risk.

Conclusion: Among patients with ACoA aneurysms, increased curvature of the A1 segment and elevated WSS on the affected side were the most robust predictors of rupture. These parameters remained significant across both univariate and multivariate analyses, underscoring their potential utility in clinical risk stratification.

Background and purpose: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) detection technique was used to screen stroke susceptibility gene methyltetrahydrofolate reductase (MTHFR), Shandong Province, to evaluate its predictive effect and clinical application value for stroke.

Methods: Sanger sequencing of MTHFR-C677T (rs 1,801,133) and A1298C (rs 1,801,131) was performed on blood samples of 635 patients with high-risk stroke, and the mutation of A1298C was detected by CRISPR. Based on the two sequencing results and the incidence of stroke, the predictive effect of MTHFR gene detection and the clinical application value of CRISPR technology were verified.

Results: Sanger sequencing revealed a statistically significant difference (p < 0.05) in MTHFR C677T mutation frequency between the stroke group and controls, and between the high-risk group and controls, indicating an association of C677T polymorphism with stroke risk. Comparison between CRISPR and Sanger results showed similar mutation detection rates across groups (26.9% vs. 26.5% in stroke/TIA/high-risk groups; both 32.6% in controls). CRISPR demonstrated 97.6% sensitivity, 98.5% specificity, 98.3% concordance, and a Kappa value of 0.956. Furthermore, homocysteine level analysis indicated significant differences (p < 0.05) in MTHFR C677T and A1298C polymorphisms between individuals with normal and high homocysteine (HHcy) in stroke‑related groups.

Conclusion: CRISPR detection technique has high accuracy and is suitable for clinical application. The increase of homocysteine level may be one of the risk factors of stroke.

Background/objective: Trigeminal neuralgia (TN) causes disabling facial pain often refractory to medication. Microvascular decompression (MVD) and percutaneous balloon compression (PBC) are established surgical options, yet their comparative efficacy and safety remain debated.

Methods: Following PRISMA guidelines, a systematic review and meta-analysis of 19 double-arm studies (2,674 patients; 1486 MVD, 1188 PBC) was performed. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were computed. Evidence certainty was graded via GRADE.

Results: MVD and PBC achieved similar initial complete pain relief (RR = 1.01, 95% CI 0.98-1.05, p = 0.49) and adequate relief (RR = 1.00, 95% CI 0.97-1.02, p = 0.67). Long-term complete (RR = 1.11, 95% CI 0.97-1.27, p = 0.13) and adequate relief (RR = 1.06, 95% CI 0.97-1.15, p = 0.17) were likewise equivalent. Pain recurrence modestly favored MVD (RR = 0.72, 95% CI 0.51-1.00, p = 0.05), while permanent complications did not differ (RR = 1.09, 95% CI 0.43-2.75, p = 0.86). Leave-one-out analyses confirmed robustness, and Egger's tests showed no publication bias. GRADE rated certainty high for initial relief, moderate for long-term outcomes and recurrence, and low for complications.

Conclusion: MVD and PBC yield equivalent short-term and long-term pain relief, as well as similar safety, in TN. MVD may offer slightly lower recurrence, whereas PBC remains advantageous for elderly or medically fragile patients. These data support the use of tailored surgical selection guided by patient comorbidity and durability expectations.

Objective: The aim of this study is to explore the mechanism by which sphingosine 1-phosphate receptor 1 (S1P1) regulates mitochondrial autophagy through PHB2, thereby exacerbating inflammation and nerve damage after epilepsy.

Methods: This study investigated the mechanisms of S1P1 and PHB2 in neuroinflammation and neuronal damage caused by epilepsy using in vitro and in vivo experiments. In vitro, a magnesium-free epilepsy model was established to induce synchronous epileptic activity. In vivo, a pilocarpine-induced epilepsy model was used with S1P1 agonists (SEW2871) and inhibitors (W146). Protein expression was analyzed by Western blotting, qPCR, and immunofluorescence for gene expression, autophagy and inflammatory markers. NBT staining measured superoxide anion production, while ATP and DCFDA assays assessed ATP and ROS levels. Patch clamp techniques measured neuronal excitability. Behavioral tests included open field tests and EEG recordings to evaluate seizure activity and behavioral deficits.

Results: PHB2 expression was significantly upregulated in epileptic astrocytes, leading to increased mitochondrial autophagy and enhanced oxidative stress. Knocking out PHB2 reduced autophagy flux and decreased pro-inflammatory cytokines, indicating its role in exacerbating inflammation. S1P1-PHB2 pathway activation upregulated both S1P1 and PHB2, promoting mitochondrial autophagy and neuroinflammation, which exacerbated epilepsy symptoms.

Conclusion: S1P1-PHB2 axis plays a crucial role in the neuroinflammation and neurodamage caused by epilepsy. S1P1, through PHB2, promotes mitochondrial autophagy, increases oxidative stress and releases pro-inflammatory cytokines, thereby leading to neural damage. By using the S1P1 antagonist W146 to inhibit autophagy and inflammatory responses, these effects can be alleviated.

Background: Invasiveness of tumor cells constitutes a major obstacle in glioma treatment. While LINC00659 has been implicated in cancer progression, its specific role and underlying mechanisms in glioma remain unclear.

Methods: LINC00659 expression in glioma cells was assessed via qPCR. Wound healing and Transwell invasion assays evaluated migratory and invasive capacities. Western blot detected alterations in EMT markers and key NF-κB pathway proteins. Molecular docking predicted LINC00659-HSP90 binding, which was validated by RIP and RNA pull-down assays. Co-IP analyzed HSP90-IKKα interaction, while genetic knockdown/overexpression models elucidated the regulatory mechanism of LINC00659 on tumor invasiveness.

Results: qPCR revealed LINC00659 upregulation in glioma cell lines. Functional assays demonstrated that LINC00659 knockdown repressed migration, invasion, and EMT. Mechanistically, LINC00659 bound to the chaperone HSP90 to stabilize IKKα protein, thereby activating NF-κB signaling. Rescue experiments confirmed the reversion of HSP90 overexpression on the anti-invasive impact of LINC00659 knockdown.

Conclusion: This study identified LINC00659 as a key promoter of glioma cell migration, invasion, and EMT, suggesting its potential as a target against glioma malignancy.

Background: Gliomas, the most common primary brain tumors, are difficult to cure because they often resist chemotherapy. This study explores the mechanisms that might regulate their resistance to the drug temozolomide (TMZ).

Methods: Based on the glioma database from TCGA, the mRNA expression levels of IFI6 and BCL11A were analyzed. GSEA was used to conduct enrichment analysis of the IFI6-related signaling pathways. The dual luciferase assay and CHIP experiment verified the binding relationship between IFI6 and BCL11A. The expression levels of IFI6, BCL11A, and ferroptosis-related proteins were detected by qPCR or WB. The drug resistance was evaluated by CCK-8 assay, clone formation assay, and flow cytometry. Lipid ROS, Fe²⁺, and MDA were used to assess the level of ferroptosis. The rescue experiments (overexpression of BCL11A combined with IFI6 or ferroptosis activator Erastin) were conducted to clarify the mechanism.

Results: IFI6 was highly expressed in glioma cells and temozolomide-resistant cells. Silencing IFI6 inhibited TMZ resistance in glioma cells. Overexpression of IFI6 reduced the level of ferroptosis in cells, which was reversed by Erastin. BCL11A, as a transcriptional repressor, directly bound to the promoter of IFI6, and its overexpression downregulated IFI6 and restored the sensitivity to TMZ. Co-overexpression of IFI6 rescued the phenotype.

Conclusion: This study reveals that BCL11A promotes ferroptosis by transcriptional inhibition of IFI6, thereby reducing TMZ resistance in glioma cells, providing a new strategy for combined targeting of IFI6 and ferroptosis.

Objectives: Neurodevelopmental and neurodegenerative disorders arise from complex disruptions in brain structure and function, many originating during early development. However, conventional in vitro and animal models often fail to capture the cellular diversity, temporal dynamics, and architectural complexity of the human brain. This review aims to synthesize recent advances in stem-cell-derived in vitro platforms, specifically brain organoids, assembloids, and organ-on-chip technologies, and evaluate how these systems are reshaping research on Alzheimer's and Parkinson's diseases by enabling more human-relevant modeling.

Methods: We surveyed recent literature focusing on region-specific and vascularized organoids, integrated neuronal subtype models, and microfluidic organ-on-chip systems. Particular attention was given to studies demonstrating increased physiological relevance, enhanced modeling of disease-specific phenotypes, and expanding utility in translational research, therapeutic screening, and drug discovery pipelines.

Results: Innovations in organoid engineering have enabled more faithful recapitulation of human brain development and degeneration. These platforms have advanced understanding of amyloid aggregation, neuroinflammatory processes, dopaminergic neuron vulnerability, and gut-brain axis contributions. The incorporation of vascular structures, improved microfluidic control, and assembly of multi-region neuronal circuits have strengthened functional readouts and boosted mechanistic insight. Collectively, these developments are accelerating preclinical therapeutic testing and enabling more predictive disease modeling.

Discussion: Compared to prior reviews, this article uniquely integrates developmental and degenerative perspectives while evaluating emerging strategies that increase reproducibility and translational accuracy. Persistent limitations, including incomplete vascularization, cellular stress responses, and batch-to-batch variability, underscore the need for improved standardization and incorporation of immune components. Future directions that merge vascular, immune, and circuit-level complexity promise to advance organoid-based neuroscience toward personalized modeling and therapeutic application.

Background: Shifting the microglia/macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype shows promise in developing therapeutic strategies after ischemic stroke (IS). The study is aimed to investigate the role of krueppel-like factor 2 (KLF2) in modulating microglia/macrophage polarization during IS.

Methods: Mice received a 60-min middle cerebral artery occlusion (MCAO) and BV-2 cells underwent oxygen-glucose deprivation/reperfusion (OGD/R) treatment to induce IS-like injury in vivo and in vitro.

Results: The mice subjected to MCAO exhibited impaired neurobehavioral performance, lower expressions of KLF2, Nrf2 and HO-1 in the peri-infarct cortex than the sham operated mice. Lentivirus-mediated KLF2 overexpression could effectively reduce the size of brain infarct, improve the recovery of neurobehavioral functions, and activate the Nrf2-HO-1 pathway in the mice subjected to MCAO. In addition, KLF2 overexpression led to M1 suppression and increase in M2 phenotype in OGD/R-insulted BV-2 microglial cells. Nrf2 knockdown was found to impair the effects of KLF2 overexpression on status of M1 and M2 phenotypes in OGD/R-insulted BV-2 cells.

Conclusion: The study unveils KLF2 is neuroprotection and could promote microglia/macrophage polarization from the M1 to M2 phenotype in IS by activating the Nrf2-HO-1 pathway.

Background: Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular event that triggers secondary brain injury in which microglial activation is central. This study explored how miR-92a-3p governs autophagy and inflammatory signaling in this context.

Methods: An in vitro ICH model was established using rat microglia exposed to hemoglobin, with lipopolysaccharide to induce autophagy. Cells were transfected with miR-92a-3p mimics or inhibitors. Apoptosis, miR-92a-3p/ATG14 expression, autophagy-related proteins (LC3, P62), and pro-inflammatory factors were assessed via molecular and cellular assays.

Results: Dual luciferase assays and ATG14 silencing confirmed direct targeting of ATG14 by miR-92a-3p. Upregulation of miR-92a-3p suppressed autophagy and thereby reduced inflammatory cytokine release, whereas inhibition of miR-92a-3p restored autophagic activity and reduced inflammation.

Conclusion: These findings establish miR-92a-3p as a critical regulator of microglial autophagy and inflammation after hemorrhagic stroke and identify it as a prospective therapeutic target for neuroinflammatory modulation.