ABSTRACT Background Approximately 30% of epilepsy patients develop pharmacoresistant epilepsy (PRE), characterized by persistent seizures refractory to antiseizure medications (ASMs). While neuroinflammation is implicated in both epileptogenesis and treatment failure, its precise temporal contribution remains unclear. This study aimed to delineate the distinct roles of acute versus chronic neuroinflammation in seizure susceptibility and the maintenance of drug resistance. Methods Male Sprague‐Dawley rats received acute inflammatory priming via systemic (intraperitoneal) or intracranial (hippocampal) lipopolysaccharide (LPS) administration prior to lithium‐pilocarpine‐induced status epilepticus (SE). Rats were subsequently classified as PRE or pharmacosensitive epilepsy (PSE) based on their response to two sequentially administered ASMs. Outcomes were assessed using video‐EEG monitoring, hippocampal cytokine profiling (IL‐6 and TNF‐α), histopathological analysis of neuronal damage, and peripheral inflammatory markers. Results Acute inflammatory priming significantly lowered the threshold for SE induction (P < 0.05); however, it did not increase the proportion of PRE (P > 0.05). In contrast, established PRE was characterized by sustained hippocampal neuroinflammation, with markedly elevated IL‐6 and TNF‐α levels compared to PSE and control groups, alongside severe neuronal loss. Conclusion These findings reveal a temporal dissociation in the roles of neuroinflammation: acute inflammation acts as a potent initiator of epileptogenesis, whereas chronic, sustained inflammation coincides with the drug‐resistant phenotype. This study refines the prevailing view of neuroinflammation from a static pathogenic factor to a dynamic, phase‐dependent modulator, supporting the rationale for stage‐targeted strategies in PRE. Notably, putative mechanisms linking inflammation to resistance, such as impaired efferocytosis, warrant future experimental validation.

Diagnosing intracerebral hemorrhage (ICH) in prehospital settings remains challenging due to unavailability of immediate neuroimaging, clinical overlap with ischemic stroke, and absence of validated circulating biomarkers for time-critical settings. Extracellular vesicles (EVs), subcellular structures capable of transporting biomolecular payloads (e.g., proteins, nucleic acids) across the blood-brain barrier, have emerged as compelling diagnostic candidates for ICH. Nevertheless, their clinical translation has been impeded by inherent biophysical heterogeneity, particularly polydisperse size distributions. To address this limitation, we engineer a steric hindrance-mediated EV analysis and size fractionation (SHEAF) platform, integrating steric hindrance-based size fractionation with membrane protein profiling to stratify EVs into three size subtypes within a 45-min workflow. Systematic evaluation using the SHEAF platform reveals that the 90 - 180 nm EV subtype exhibits superior discriminative capacity in differentiating ICH from ischemic stroke plasma specimens. This technology not only advances rapid prehospital ICH diagnostics but also establishes a method for elucidating size-dependent EV functionalities across neurological pathologies.

Epilepsy affects about 1% of the global population, with 30% of patients developing pharmacoresistant epilepsy (PRE). The underlying causes of PRE remain elusive. However, there is suspicion that neuroinflammation may cause recurrent epilepsy by activating the mitogen and stress-activated protein kinase 1 (MSK1)/cAMP response element-binding protein (CREB) signaling pathway. Our study integrates clinical, cellular, and animal research to explore this link. We found that MSK1 and CREB expression significantly increased in epileptic patients and model rats after seizures, with interactions observed both in vivo and in vitro. Inflammatory factors correlated with epilepsy in both patient and rat populations, showing a significant increase in neuroinflammatory markers in those with PRE. However, MSK1 intervention had limited effects on neuroinflammatory factor expression. Interestingly, inflammation activates the MSK1/CREB pathway in rat hippocampal neurons, suggesting that neuroinflammation promotes seizure and PRE formation via MSK1-mediated CREB activation. Our study highlights the potential of targeting the MSK1/CREB pathway to develop novel therapeutic approaches for PRE, offering hope for improved clinical outcomes in epilepsy management.

Secondary injury following intracerebral hemorrhage (ICH) is a primary cause of patient mortality and disability. Its mechanisms involve disturbances in multiple metabolic processes, among which lipid metabolism is closely associated with cellular damage. This study aims to identify candidate biomarkers for ICH by focusing on lipid metabolism. Lipid metabolism activity was evaluated at the single-cell level using Single-Sample Gene Set Enrichment Analysis (ssGSEA). Key biomarkers were subsequently identified by integrating differential expression analysis with multiple machine learning algorithms. Their functional properties were systematically characterized through enrichment analysis, regulatory network construction, cell–cell communication, and drug prediction. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot were performed on rat brain tissue to validate the expression of key biomarkers. A total of 15 cell subpopulations belonging to 8 cell types were identified in the scRNA-seq data. Neuron-derived damaged/dying cells exhibited the most active expression of lipid metabolism genes. Solute carrier family 25 member 45 (SLC25A45) and cell adhesion molecule 1 (CADM1) were further identified as key biomarkers for lipid metabolism in ICH. Gene Set Enrichment Analysis (GSEA) revealed distinct functional associations for the two genes: CADM1 was predominantly linked to metabolic processes, whereas SLC25A45 was significantly associated with proteasomal activity, immune signaling pathways, and the pathogenesis of major neurodegenerative disorders. The high and low expression of these two genes both exhibited extensive cellular communication. By constructing a gene regulatory network, v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) and CCCTC-binding factor (CTCF) were identified as common transcription factors (TFs) for the two key biomarkers, and the long non-coding RNAs (lncRNAs), including nuclear paraspeckle assembly transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), have close regulatory relationships with CADM1. Drug sensitivity prediction based on the key biomarkers suggested Vancomycin Hydrochloride and Zinc Sulfate as potential therapeutic drugs for ICH. SLC25A45 and CADM1 are key biomarkers in lipid metabolism during ICH, representing promising candidates for further investigation.

This study was designed to explore the effects of esketamine on cognitive deficits and blood-brain barrier (BBB) dysfunction in sepsis-associated encephalopathy (SAE). An in vivo SAE model was generated through the administration of lipopolysaccharide (LPS), and LPS-induced cognitive impairment in rats was evaluated using the Morris water maze (MWM) test. BBB disruption in vivo was assessed by measuring brain water content together with Evans blue dye penetration, while LPS-induced endothelial hyperpermeability in vitro was examined through FITC-dextran leakage. The protein expression of claudin-3 and ZO-1 was determined by western blotting. In addition, the levels of pro-inflammatory cytokines, cell apoptosis, autophagy, and the activity of the BDNF/TrkB pathway were examined. Rapamycin (Rap, an autophagy inducer) and K252a (a BDNF inhibitor) were used to determine whether the protective effects of esketamine were associated with autophagy and BDNF/TrkB signaling. Esketamine treatment significantly improved the LPS-induced cognitive dysfunction and neurological injury observed in vivo, and it also inhibited the production of pro-inflammatory cytokines and reduced cell apoptosis both in vivo and in LPS-treated hCMEC/D3 cells. Importantly, esketamine alleviated BBB hyperpermeability in vivo and prevented LPS-induced endothelial leakage in vitro. Moreover, esketamine suppressed LPS-induced autophagy, and the influence of esketamine on claudin-3 and ZO-1 expression was reversed when Rap was applied. Esketamine activated the BDNF/TrkB pathway, and the protective effects of esketamine on BBB integrity and autophagy in response to LPS were abolished by K252a. Taken together, these findings indicate that esketamine protects the BBB against SAE by activating the BDNF/TrkB pathway and inhibiting autophagy, providing a potential therapeutic strategy for SAE.

Background Endoscopic surgery (ES) and stereotactic aspiration (SA) are minimally invasive surgical techniques. This study was conducted to investigate the differences between ES and SA in terms of perioperative perihematomal edema (PHE) and evaluate the relationship between perioperative PHE volumes and long-term functional dependence. Methods The clinical data of 199 patients with supratentorial spontaneous intracerebral hemorrhage were collected from January 2018 to August 2024, and 1:1 matching was applied using propensity scores. Confounding factors were excluded, and the final ES and SA groups each comprised 84 patients. Three-dimensional PHE volume measurements were conducted using 3D Slicer. The perioperative dynamics of the two patient groups were then assessed via a longitudinal comparative analysis. Results At 3 and 7 days, the ES group demonstrated markedly higher postoperative PHE volumes and greater postoperative mass effect volumes than the SA group. However, the ES group exhibited significantly lower postoperative hematoma volumes and lower postoperative mass effect volumes at 6 hours and 1 day (p < 0.001). The multivariate analysis revealed that postoperative mass effect volume at 7 days was a significant predictor of poor prognosis. Conclusion Endoscopic surgery may lead to lower PHE and mass effect volumes at 6 hours after surgery, but higher PHE volumes after 3 days. In contrast, stereotactic aspiration is associated with lower PHE and mass effect volumes over 7 days. Additionally, the postoperative mass effect volume at 7 days was identified as a significant independent risk factor for poor long-term functional outcomes.

Spontaneous thalamic hemorrhage (TH) is associated with substantial morbidity and mortality. The optimal hematoma volume (HV) thresholds for prognostic stratification and the comparative effectiveness of minimally invasive surgery (MIS) versus conservative treatment remain uncertain. We retrospectively analyzed consecutive patients with spontaneous TH admitted to a comprehensive stroke center n = 436 using a two-stage design. Stage 1: In the conservatively treated cohort n = 280, predictors of poor 90-day functional outcome (modified Rankin Scale [mRS] 3–6) were identified using multivariable logistic regression; a prognostic nomogram was constructed and validated. Receiver operating characteristic (ROC) analyses were used to determine HV cutoffs for predicting poor functional outcome and mortality. Stage 2: Patients with HV ≥ 7 mL were included in a comparative effectiveness analysis of MIS versus conservative treatment n = 208. Propensity score matching (PSM) was performed (1:1 nearest-neighbor without replacement; caliper = 0.2 SD of the logit of the propensity score) to balance baseline covariates, including age, sex, systolic blood pressure (SBP), Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), intraventricular hemorrhage (IVH), Graeb score, and HV. In conservatively treated patients n = 280, older age, higher SBP, and larger HV were independently associated with increased odds of poor 90-day outcome, whereas higher GCS was protective. The nomogram demonstrated good performance. ROC analyses identified 7 mL as the optimal HV cutoff for predicting poor functional outcome AUC = 0.86, and 13 mL for predicting mortality AUC = 0.81. After PSM in patients with HV ≥ 7 mL (n = 102; 51 matched pairs), MIS was associated with lower 90-day mortality compared with conservative treatment 9.8

Background:Primary central nervous system T-cell lymphoma (PCNSTL) is an exceptionally rare central nervous system lymphoma with limited clinical data. We present a large case review series of PCNSTL to summarise the clinical characteristics of this disease. Methods:This study integrated 4 new cases of PCNSTL from our centre with 132 previously reported cases identified through a systematic search of PubMed, Cochrane Library and Web of Science databases. Results:A total of 136 PCNSTL cases were identified, with a median age of 41 years (range 2-89 years), and a male-to-female ratio of 1.8:1. Peripheral T-cell lymphoma-not otherwise specified was the most prevalent pathological subtype. Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK+ALCL) predominated in men relative to the various subtypes. The cerebral hemispheres are the most frequent anatomical region involved (71.3%), followed by cerebellum (16.2%), basal ganglia (14.7%), brainstem (14.7%), meninges (11.8%) and corpus callosum (2.9%). Meningeal involvement was observed in nearly 50% of ALCL cases. Histopathologically, 31.8% of tumour cells (29/91) were small cell-dominated, 79.2% of the cases presented angiocentric growth pattern (57/72), and half of cases had a positive finding of cerebrospinal fluid (CSF) flow cytometry (7/14). Conclusions:PCNSTL has a male predilection, particularly in ALK+ALCL. PCNSTL shows reduced basal ganglia and corpus callosum involvement relative to primary central nervous system B-cell lymphoma, but displays heightened meningeal tropism, especially in ALCL cases. Histopathological examination typically reveals prominent perivascular lymphocytic cuffing in PCNSTL. CSF flow cytometry could be considered a preferred method for a definite diagnosis of PCNSTL when brain biopsy is not possible.

Introduction:Mild ischemic stroke accounts for over half of all stroke cases, yet how peripheral immune responses evolve over time-and how they differ by infarct location-remains poorly defined. Methods:Peripheral blood was collected from ten patients with mild ischemic stroke and five matched controls at days 1, 3, and 7 after onset. Patients were stratified by cortical or subcortical infarction. High-dimensional mass cytometry was used to characterize immune cell composition and immune checkpoint expression. Results:Subcortical infarction was associated with sustained expansion of classical monocytes, persistent reduction of intermediate monocytes, and delayed PD-1/PD-L1 regulatory signaling, indicating prolonged myeloid-driven inflammation. In contrast, cortical infarction exhibited a more balanced monocyte profile and earlier PD-1 upregulation on dendritic cells and classical monocytes. CD4⁺ and CD8⁺ T-cell subsets showed distinct, location-dependent dynamics: cortical infarction induced earlier modulation of memory and regulatory phenotypes, whereas subcortical infarction produced slower but more persistent shifts. CCR5-defined CD8⁺ T-cell subsets also differed markedly, with subcortical infarction showing enrichment of CCR5⁺ effector cells, reduced checkpoint expression, and contraction of the CCR5⁻ compartment. Discussion:Peripheral immune remodeling in mild ischemic stroke displays clear infarct location-specific trajectories. These findings highlight infarct topology as a critical determinant of post-stroke immune regulation and support the development of location-adapted immunomodulatory strategies.

Background Intracerebral hemorrhage (ICH) is a severe subtype of stroke. There are currently no specific treatment strategies for secondary brain injury and neurological deficits following ICH. Copper (Cu) is an essential cofactor for all living organisms. Cytotoxicity can occur when copper ion concentration exceeds the homeostatic threshold, leading to cell death. However, the relationship between copper and ICH is unclear. Methods In vivo, an ICH model was established in male Sprague-Dawley rats by stereotactically injecting autologous blood into the right basal ganglia. In vitro, we employed hemin and CuCl2 to simulate ICH conditions and induce cuproptosis in BV2 microglial cells. To investigate the role of copper in brain injury and neuronal damage, we administered the copper chelator tetrathiomolybdate (TTM) and knocked down the essential cuproptosis gene ferredoxin 1 (FDX1). Results Our findings demonstrate that following ICH, elevated copper levels and FDX1 expression, low expression of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and lipoic acid synthetase (LIAS), loss of mitochondrial membrane potential and neuronal impairment (increased growth associated protein 43 (GAP43) and decreased microtubule associated protein 2 (MAP2) expression), ultimately lead to neuronal death. Both TTM and si-FDX1 treatment attenuated the copper overload and inhibited cuproptosis, thereby ameliorating the ICH-induced phenotype. Conclusion Copper depletion attenuates ICH-induced neuronal damage by inhibiting cuproptosis, highlighting a potential therapeutic strategy for mitigating secondary brain injury and neuronal damage following ICH.

BackgroundIntracerebral hemorrhage (ICH) is the most lethal subtype of stroke, yet effective disease-modifying therapies remain limited. Beyond the primary mechanical insult, dysregulated neuroinflammation is thought to be a major contributor to hematoma expansion, perihematomal edema, and secondary neuronal injury. Natural killer T (NKT) cells, a specialized population of lipid-reactive lymphocytes linking innate and adaptive immunity, have emerged as potentially relevant immunoregulatory contributors to the post-hemorrhagic response.Main bodyThis review summarizes current experimental evidence, together with the still limited clinical data, regarding the biology of NKT cells in ICH, including their development, subset heterogeneity (type I invariant, type II, and regulatory NKT-like programs), and activation through CD1d-restricted lipid antigens and cytokine-driven pathways. Available evidence supports a phase-dependent working model of NKT-cell function in ICH. In the acute stage, type I iNKT-associated responses may amplify neuroinflammation through IFN-γ- and TNF-α-related signaling, thereby contributing to myeloid activation, blood-brain barrier (BBB) dysfunction, and neutrophil recruitment. In later stages, regulatory NKT-associated programs, including type II NKT- or NKT10-like responses, may become increasingly linked to IL-4-, IL-13-, and IL-10-related pathways that support pro-resolving myeloid phenotypes, hematoma clearance, and tissue repair. In addition, NKT cells may influence broader immune networks, including T-cell responses and, more speculatively, B-cell-associated pathways. We also discuss emerging therapeutic strategies targeting NKT-cell biology, including α-GalCer-based ligands, anti-CD1d/TCR approaches, sphingosine-1-phosphate (S1P) receptor modulators, and PPAR-γ agonists, while emphasizing the importance of treatment timing, delivery, and subset specificity.ConclusionCurrent evidence suggests that NKT cells may exert both detrimental and beneficial effects during ICH progression, with their impact varying according to disease stage and microenvironmental context. Their rapid responsiveness and functional plasticity make them promising, though still incompletely validated, targets for phase-tailored immunomodulation. Future progress will depend on high-resolution profiling to better define therapeutic windows, clarify subset-specific functions, and support the development of interventions that more precisely balance inflammatory control with tissue repair.

Background and purposeThe mortality rate of spontaneous cerebellar hemorrhage (SCH) is extremely high. Currently, only surgical treatment (ST) and conservative treatment (CT) methods are available; however, the indications for the treatment of SCH are not yet clear. In this study, we compared the outcomes of conservative and surgical treatment methods for patients with SCH and a hematoma volume of >10 mL.MethodsWe retrospectively included patients with SCH who were treated in the Emergency Department of the Affiliated Hospital of Guizhou Medical University, the Neurosurgery Department of the Affiliated Jinyang Hospital of Guizhou Medical University, and the Neurosurgery Department of the Second Affiliated Hospital of Guizhou Medical University from April 2014 to January 2024. Patients were divided into CT group and ST group using a 1:2 stratified matching method based on hematoma volume and diameter. We collected baseline clinical characteristics of patients, including age, blood pressure, imaging data, complications, and prognosis, and conducted univariate analysis. After excluding factors with collinearity effects through collinearity diagnosis, we used a binary logistic regression model to analyze the independent correlation between good and poor prognosis.ResultsBased on the inclusion criteria, 98 patients with SCH were screened, comprising 41 patients in the CT group and 57 patients in the ST group. Univariate analysis showed that the ST group had a higher proportion of patients with good prognosis at 1 and 3 months [41(71.9%) vs. 19(46.3%), p = 0.010], [34(59.6%) vs. 14(34.1%), p = 0.013], and a lower mortality rate than the CT group [10(17.9%) vs. 15(39.5%), p = 0.020]. SCH is further divided into a 1-month good prognosis group and a poor prognosis group, and a 3-month good prognosis group and a poor prognosis group. After excluding factors through collinearity diagnosis, the results of multivariate binary logistic regression analysis showed that surgical treatment had better 1- and 3-month prognosis than conservative treatment in SCH patients (OR: 4.898, 95% CI: 1.559–15.388, p = 0.007, OR: 3.965, 95% CI: 1.429–11.004, p = 0.008).ConclusionWhen the bleeding volume of SCH patients is greater than 10 mL, surgery is an independent predictor of good short-term prognosis.

Ischemic stroke is an acute neurological emergency caused by cerebral blood flow obstruction, with current diagnosis heavily dependent on time-consuming neuroimaging techniques that often delay critical intervention. Extracellular vesicles (EVs) have emerged as promising biomarker carriers for brain disorders due to their ability to cross the blood-brain barrier, yet their clinical translation has been hindered by complex isolation and detection requirements. Here, we develop a novel wash-free analytical platform leveraging liposome-EV fusion mediated by membrane lipid fluidity and integrated with Förster resonance energy transfer (FRET) technology. This innovative approach enables direct, rapid quantification of both EV concentration and EV-encapsulated miRNA in native biofluids without requiring prior EV separation, overcoming key limitations of conventional methods. When applied to clinical plasma samples, our method demonstrated high sensitivity with detection limits of 4.272 × 1011 particle/mL for EVs and 0.779 nM for miRNA. While no significant difference in total EV concentration was observed between ischemic stroke patients and hypertensive controls, EV-derived miRNA-21 levels were markedly elevated in patient samples, showing exceptional diagnostic performance (AUC = 0.915). This fusion-mediated FRET platform represents a significant advancement in EV-based diagnostics, offering a rapid, sensitive tool with substantial potential for point-of-care stroke diagnosis and timely intervention.

The high mortality and disability rates associated with spontaneous intracerebral hemorrhage (sICH) are primarily attributed to secondary injuries caused by hematoma expansion from continuous bleeding or rehemorrhage. Rapid hemostasis to prevent hematoma progression is critical in clinical emergencies for improving surgical outcomes and patient prognosis. For internal hemorrhages inaccessible to external interventions, especially for sICH, intravenous hemostatic strategies are essential regardless of ultimate surgical eligibility. This study reported a stealth hemostatic anchor system based on peptide-drug conjugates. Tranexamic acid (TXA), a clinically approved antifibrinolytic agent, served as the hemostatic component, while a von Willebrand factor (vMF)-binding peptide (VBP) enabled targeted delivery by specifically binding to (vMF) exposed at vascular injury sites. A plasmin-cleavable linker was incorporated to control TXA release, ensuring site-specific drug activation. The plasmin-responsive peptide-drug conjugate (RPDC) was synthesized by covalently linking TXA to VBP via the plasmin-cleavable linker. In vitro and in vivo experiments verified the targeted hemostatic efficacy of RPDC, especially demonstrating 42% reduction in hematoma volume (P < 0.001 vs. saline; P < 0.05 vs. free TXA) with mitigated peri‑hematomal pathology in the collagenase-induced ICR mouse ICH model. These results highlight the potential of the stealth hemostatic anchor as a precision therapeutic strategy for managing sICH, particularly in cases of internal hemorrhages inaccessible to surgical intervention or visual inspection. The plasmin-dependent targeting mechanism enables precise drug localization at cryptic hemorrhage sites, but further studies in larger animal models are needed to confirm its efficacy. This design offers a theoretical framework for advancing emergency interventions in cerebral hemorrhage and addressing challenges related to inaccessible bleeding sites.

Intracerebral hemorrhage (ICH) leads to perihematomal edema (PHE), exacerbating brain swelling and functional deterioration. Blood–brain barrier disruption has been observed in carriers of the apolipoprotein E (APOE) ε4 genotype. The study focused on the impact of APOE ε4 in PHE and its underlying molecular mechanisms. This study was a single-center, prospective, and nested cohort study involving patients with ICH admitted to the emergency department of the Affiliated Hospital of Guizhou Medical University between April 2023 and October 2024. We included patients who underwent surgery within 24 h of onset. APOE ε4 and APOE ε3 groups were formed based on hemorrhage location, age, and hemorrhage volume using a 1:1 stratified matching method. We analyzed the initial cranial computed tomography scans taken within 24 h after onset; we measured hematoma volume and edema volume (EV) and calculated the combined edema and hematoma volume, the preoperative edema coefficient (PEC), and the edema expansion distance (EED). In addition, cerebrospinal fluid samples from the hematoma cavity were collected during surgery, and enzyme-linked immunosorbent assays were used to measure the expression levels of APOE, low-density lipoprotein receptor-related protein 1 (LRP1), cyclophilin A (CypA), nuclear factor κB (NF-κB), matrix metalloproteinase 9 (MMP-9), occludin, and ZO-1. Among 48 patients (24 per group), APOE ε4 carriers exhibited greater PHE than APOE ε3 carriers, reflected by increased EV, PEC, and EED. After adjusting for hematoma volume, linear regression showed APOE ε4, MMP-9, and occludin were positively associated with PEC, whereas LRP1 had an inverse relationship (β = − 0.2, p = 0.008). Mediation analysis revealed APOE ε4 influenced PEC indirectly via MMP-9 (effect size = 0.38, p < 0.001), accounting for 32.84

OBJECTIVES: The evaluation of hypomagnesemia's significance in predicting the presence of the black hole sign in patients with intracranial hemorrhage is currently under investigation. METHODS: The study included 261 patients with cerebral hemorrhage who underwent initial skull computed tomography within 24 hours of admission. Sixty-nine patients (26.4%) exhibited hypomagnesemia in the initial laboratory examinations. The black hole sign was observed in 123 patients (referred to as the black hole sign group, which includes patients with and without hypomagnesemia), while the remaining 138 patients (nonblack hole sign group) did not exhibit this feature. The values of hypomagnesemia were assessed through multivariable logistic regression analyses. RESULTS: The black hole sign occurred in 45 of the 69 (65.2%) patients with hypomagnesemia, and in 78 of the 192 (40.6%) patients without hypomagnesemia. In the black hole sign group, hypomagnesemia was observed in 45 patients (36.6%). However, only 24 patients (19.5%) from the normal magnesium concentration group exhibited hypomagnesemia. The sensitivity, specificity, and positive and negative predictive values of hypomagnesemia for predicting the black hole sign were 69.9%, 82.5%, 36.6%, and 82.8%, respectively. The odds ratios for hypomagnesemia, smoking history, and hypokalemia in predicting the presence of the black hole sign were 2.74, 1.971, and 1.629, correspondingly. CONCLUSIONS: The presence of hypomagnesemia may serve as a predictive factor for the black hole sign and rebleeding in patients with intracerebral hemorrhage, thereby providing valuable guidance for clinical treatment.

In recent years, extracellular vesicles (EVs) have been extensively investigated as circulating biomarkers for non-invasive glioma diagnosis due to their ability to traverse the blood-brain barrier while carrying abundant biomolecules. However, the high heterogeneity of EVs in blood circulation, attributed to their diverse cellular origins, poses challenges in isolating cancer cell-secreted EVs using current sorting methods. To address this issue, aptamer-modified magnetic nanoparticles and photosensitizer-conjugated aptamer probes were employed to achieve single-step orthogonal sorting of dual-protein positive EVs within 1 h. Integrated with a nicking endonuclease-amplified giant magneto resistance (GMR) biochip, the platform enabled ultrasensitive miRNA profiling with a detection limit of 1.88 x 10(5) copy/mL. Utilizing this platform, we revealed EGFR+/CD133 + EV miRNA signatures could effectively distinguished glioma patients from healthy controls and other brain disorders with area under curve scores of 0.948 and 0.906, respectively. The system combines rapid analysis (<2.5 h), minimal sample input (50 mu L plasma), and amplified detection, establishing an advanced liquid biopsy technology for neuro-oncology.

Intracerebral hemorrhage (ICH) poses significant disability and mortality risks and perihematomal edema (PHE) plays a crucial role in ICH prognosis. The ApoE-ε4 allele has been implicated in exacerbating PHE and influencing neurological recovery post-ICH, yet, this specific association has not been explored much. This study aimed to investigate the correlation between ApoE-ε4 allele, PHE, and clinical prognosis in patients with ICH. We conducted a prospective observational cohort study at the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2023. We enrolled patients with supratentorial ICH patients and analyzed ApoE gene alleles, clinical baseline data, blood biochemical indices, and imaging findings. We considered ApoE-ε4 carrier status as an exposure variable and compared PHE volumes between ApoE-ε3 (ε3/ε3) and ApoE-ε4 (ε2/ε4, ε3/ε4, ε4/ε4) carriers. We also compared clinical and imaging characteristics between the good prognosis group (modified Rankin score 0–3) and the poor prognosis group (modified Rankin score 4–6). Finally, we examined the association between ApoEε4 and PHE volume and poor prognosis at discharge. Among 153 patients, 63 (41%) carried ApoE-ε4. ApoE-ε4 carriers had significantly higher PHE volumes at 24 h and on days 5–7 compared to ApoE-ε3 carriers. The poor prognosis group had a higher proportion of ApoE-ε4 carriers (53.9% vs. 28.6%, p = 0.001) and increased PHE volumes. ApoE-ε4 (OR 2.438, p = 0.02) and PHE (OR 1.048, p = 0.015) were independent predictors of poor prognosis. The area under the curve for ApoE-ε4 was 0.627, and for PHE volume, it was 0.698. The ICH patients carrying the ApoE-ε4 allele show severe PHE and poorer outcomes. Carrying ApoE-ε4 gene is an independent predictor for poor outcomes in patients with ICH. Trial registration: ClinicalTrials.gov, NCT05687201. Registered June 1, 2023, Effect of Apolipoprotein E on the Prognosis of Patients with Intracerebral Hemorrhage—Full Text View—ClinicalTrials.gov “prospective registered”.

Drug-resistant epilepsy (DRE) is frequently characterized by pathological mossy fiber sprouting (MFS), which is a defining indicator of aberrant synaptic remodeling within the hippocampus. Despite extensive investigations of the molecular underpinnings of MFS, they remain only partially elucidated. Synaptic vesicle protein 2 A (SV2A) is a key modulator of neurotransmitter exocytosis that has been associated with epileptogenesis. However, its involvement in structural neural plasticity throughout epileptogenic progression remains unclear. In this study, a pilocarpine-induced rat model of DRE was utilized to evaluate the influence of SV2A on MFS. Immunofluorescence, western blot analysis, and the lentivirus-mediated modulation of SV2A expression revealed that SV2A suppression intensified both MFS and seizure severity. Mechanistically, the results of co-immunoprecipitation combined with mass spectrometry suggested that a deficiency of SV2A could facilitate aberrant axonal sprouting via disruption of the laminin α5 (LAMA5)/integrin β1 (ITGB1) signaling cascade. Subsequent validation confirmed that decreased LAMA5 expression and attenuated ITGB1 activation in SV2A-deficient rats were contributory factors to pathological axonal sprouting. These findings implicate SV2A as a critical determinant of structural plasticity in epileptogenesis and highlight the LAMA5/ITGB1 axis as a promising therapeutic avenue for DRE.

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and disability. Cuproptosis is a regulatory cell death modality dependent on intracellular copper ion concentration, the role of which in ICH is unclear. Upon activation by ligand agonists, peroxisome proliferator-activated receptor-γ (PPARγ), can alleviate brain injury after ICH. To investigate the inhibitory effect of activating PPARγ on cuproptosis following ICH, we established the ICH model in vivo and in vitro and they were treated with the PPARγ agonist or antagonist after models being established successfully. Then, the copper ion concentration was measured by copper colorimetric assay and the expression of cuproptosis-related regulatory factors and copper transporter 1 was detected by western blotting and immunofluorescence staining (except in the cell level). We found that the increase in copper ion concentration following ICH leads to the disruption of copper homeostasis, inducing cuproptosis via copper toxicity. Activating PPARγ regulates the expression of cuproptosis-associated positive or negative regulatory factors and mitigates copper toxicity by inhibiting the influx of copper ions into the cell, thereby inhibiting cuproptosis. This study not only reveals the relationship between ICH and cuproptosis but also may provide new therapeutic strategies for improving the prognosis of patients with ICH.