Brain-computer interface (BCI) control inefficiency often occurs in stroke survivors due to insufficient sensorimotor activity generated during motor imagery. Previous studies focused on upregulating excitability of primary motor cortex (M1) alone. Dorsolateral prefrontal cortex (DLPFC), an important region for motor imagery, may be effective for improving BCI performance. This study is aimed at investigating how intermittent theta burst stimulation (iTBS) targeted on M1 and DLPFC influences BCI performance and its neural mechanisms.25 healthy subjects (9 males) received four types of iTBS (i.e., M1 iTBS, DLPFC iTBS, combination of M1 and DLPFC iTBS and sham iTBS) on separate days. BCI control testing, functional near-infrared spectroscopy assessment and single-pulse transcranial magnetic stimulation were performed before and immediately after iTBS in each session. Corticospinal excitability, brain activation, and functional connectivity were calculated. Our results revealed that corticospinal excitability was significantly increased after M1 iTBS (P = 0.016), with the magnitude of increase positively correlated with BCI performance (P = 0.013). Frontoparietal network functional connectivity was significantly increased after DLPFC iTBS (P's<0.05), with the magnitude of increase positively correlated with changes in BCI performance (P's<0.05). In conclusion, M1 iTBS and DLPFC iTBS alone influences BCI performance through specific neural mechanisms, and the combination of M1 and DLPFC iTBS did not induce any significant results. M1 iTBS could influence BCI performance by enhancing corticospinal excitability, while DLPFC iTBS could influence BCI performance by increasing frontoparietal network connectivity. These findings could contribute to the advancement of novel therapeutic strategies aimed at enhancing BCI effectiveness for neurological populations. Trial registration: The study was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2500097678). Registration Date: 2025-02-24.

Background Long-term outcomes after endovascular thrombectomy (EVT) and the role of adjunctive neuroprotection to achieve post-stroke independence remain incompletely characterized. In this hypothesis-generating target-trial emulation, we assessed 12-month functional outcomes in a prespecified extension of a propensity score-matched cohort of rigorously selected EVT patients treated with adjunctive Cerebrolysin, a multimodal neuroprotective agent. Methods Consecutive EVT patients were prospectively enrolled and treated with Cerebrolysin 30 mL/day for 21 days starting immediately post-EVT, with a second 21-day course at 69-90 days. Outcomes were compared with historical controls using 1:1 nearest-neighbor propensity score matching on ten prespecified covariates. The primary endpoint was functional independence (modified Rankin Scale [mRS] 0-2) at 12 months. Secondary endpoints included 12-month mRS shift, Barthel Index (BI), and need for institutional care. Multivariable regression models were used to estimate adjusted associations, with prespecified sensitivity analyses including calendar time and key EVT predictors. Results Cerebrolysin use was associated with higher odds of 12-month functional independence after adjustment for potential confounders (aOR 6.10, 95% CI 1.64-22.66; p<0.01) and a favorable shift toward lower disability across the 12-month mRS distribution (common OR for favorable shift 3.57, 95% CI 1.42-8.93; p<0.01). Cumulative 12-month mortality was similar between groups (both 18%). Among survivors, 6% of the Cerebrolysin group versus 19% of controls required institutional care (unadjusted OR 0.26; 95% CI 0.07-0.99; NNT 8). BI scores were higher in the Cerebrolysin group than in controls (median (Q1-Q3) 92 (82-100) vs 83 (73-93); p=0.01). In multivariable models, Cerebrolysin remained associated with 12-month independence alongside complete reperfusion (mTICI 3), lower post-EVT NIHSS, fewer device passes, and absence of symptomatic intracranial hemorrhage. Conclusions In EVT-treated patients selected for a small infarct core, robust collaterals, and high-quality reperfusion, adjunctive Cerebrolysin showed a potential benefit toward better 12-month functional outcomes. These exploratory findings require confirmation in multicenter randomized trials to establish efficacy and refine patient selection.

Intracranial aneurysms (IAs) are severe cerebrovascular disorders lacking effective gene therapy or pharmacological interventions. Vascular smooth muscle cell (VSMC) senescence has been associated with various cardiovascular and cerebrovascular diseases; however, its role in IA pathogenesis remains unexplored, and the key regulatory genes remain unidentified. By integrating multi-omics data, machine learning, and experimental validation, we identified two senescence-associated genes (SAGs) that may serve as VSMC senescence biomarkers in IAs. We integrated single-cell RNA sequencing data from a mouse elastase-induced IA model (GSE193533) with human bulk RNA sequencing and microarray datasets to investigate VSMC senescence in IA. Our analyses included cell clustering, cell-cell communication, differential expression, functional enrichment, pseudotime trajectory inference, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). Machine learning identified candidate SAGs, which were validated using external datasets and immunohistochemical analysis of human IA tissues. Single-cell analysis of the mouse IA model revealed 26 clusters across 10 cell types, with IA samples showing VSMC depletion, immune cell enrichment, and fibroblast expansion. VSMCs were categorized into five subsets (VSMC1-5), with the extracellular matrix remodeling and synthetic-inflammatory subtype (VSMC1) significantly increased. Differential expression analysis of VSMCs intersecting with senescence-associated genes from the Aging Atlas database identified 159 SAGs enriched in inflammatory and apoptotic pathways. Integrating hdWGCNA and bulk transcriptomics identified 45 key SAGs. TGFB1 and SERPINE1 emerged as robust biomarkers of senescence-associated VSMCs, showing high diagnostic accuracy (AUC > 0.75) and upregulation in IA tissues. Our study provides new insights into the pathological mechanisms of intracranial aneurysms. VSMC senescence may contribute to IA progression. TGFB1 and SERPINE1 may serve as biomarkers and promising therapeutic targets for VSMC senescence in IA. However, their specific mechanisms require further investigation and validation.

This study investigated the therapeutic potential of skin-derived precursor Schwann cells (SKP-SCs) for secondary brain injury following intracerebral hemorrhage (ICH) and its underlying mechanisms. An ICH model was established in mice via intrastriatal autologous blood injection. SKP-SCs were administered intranasally 24h post-ICH, with the AKT inhibitor GDC0068 used for intervention. Results demonstrated that transplanted SKP-SCs survived peri-hematomally, significantly improved short- and long-term neurological function, reduced brain tissue damage and neuronal apoptosis, preserved blood-brain barrier integrity, and suppressed microglial/macrophage activation and neutrophil infiltration. Mechanistically, SKP-SCs exerted neuroprotection by activating the PI3K/AKT/FOXO3a signaling pathway. In conclusion, intranasal SKP-SC transplantation alleviates ICH-induced deficits and secondary injury via this pathway, representing a promising therapeutic strategy during the acute phase following ICH.

Clarifying the critical lesion regions of poststroke cognitive impairment (PSCI) could improve the understanding of how anatomical locations and functional networks jointly influence the manifestation of cognitive deficits. Lesion-symptom and lesion network analyses are performed to identify the anatomical sites and functional networks related to specific cognitive functions. The multidomain cognitive statuses and the focal brain lesions of 83 patients with PSCI were recorded during the acute poststroke period (< 2 weeks). Multivariate lesion-symptom mapping was performed to identify risk regions, i.e., lesion sites associated with worse cognitive deficits; functional lesion network mapping was performed to identify risk networks, i.e., brain networks connected to risk regional peaks. Lesion-symptom mapping analysis identified several brain regions where lesions were significantly correlated with neurological deficit, general cognitive impairment, visuospatial dysfunction, and executive dysfunction. Various types of cognitive deficits presented diverse risk region distribution patterns with different peaks. Functional lesion network mapping demonstrated that networks connected to peak risk regions for neurological deficit and general cognitive impairment were mostly similar to the default network (DN), whereas the risk network for visuospatial and executive dysfunctions was the somatomotor network (SN). Functional imaging measurements directly from PSCI patients revealed that intranetwork functional connections within the limbic network, which is functionally similar to the DN, were stably reduced in all patients, and intranetwork functional connections in the SN exhibited the same pattern. Although the decreases did not present the network preference observed in lesion network mapping, these results still support the concept that lesions to specific nodes of the DN or SN are associated with the cognitive deficits that constitute PSCI.

Ischemic stroke is one of the leading causes of disability and mortality worldwide. Its pathogenesis extends beyond focal cerebral ischemia-induced neuronal injury, encompassing profound immune dysregulation and secondary inflammatory responses. Recent studies have highlighted T cell dysfunction, particularly T cell exhaustion, as a critical driver of post-stroke immunosuppression and increased susceptibility to infection. However, the molecular mechanisms underlying this process remain unclear. This study focuses on a novel immunoregulatory axis involving cuproptosis, metabolic reprogramming, and T cell exhaustion, and systematically investigates the role of the key regulatory molecule TCIRG1 in post-ischemic immune homeostasis disruption. Through integrative analysis of human peripheral blood transcriptomic data (GSE58294) and single-cell transcriptomic datasets from mouse brain and bone marrow following middle cerebral artery occlusion (MCAO) (GSE174574 and GSE293098), we found that the cuproptosis pathway was markedly activated after ischemic stroke. Notably, TCIRG1 was highly expressed in T cells and co-upregulated with the cuproptosis regulator Fdx1 and T cell exhaustion markers. Metabolic flux analysis revealed that high TCIRG1 expression was associated with enhanced pyruvate metabolism and was accompanied by downregulation of MYC signaling and upregulation of Zfp644, suggesting a role for TCIRG1 in driving T cell exhaustion through metabolic reprogramming. Furthermore, CellChat analysis indicated that TCIRG1 altered intercellular communication between T cells and microglia, thereby reshaping the local immune communication network. Collectively, these findings suggest that TCIRG1 may promote T cell dysfunction via cuproptosis and metabolic pathways, contributing to immune microenvironmental imbalance after ischemic stroke. This study proposes a novel multi-axis regulatory model and provides a potential molecular target for post-stroke immunotherapy.

A gap in developing novel preclinical treatment strategies for ischemic stroke is predicting long-term outcome in experimental stroke models early during ischemia to reduce heterogeneity and sample size. Besides saving costs through improved risk stratification, reducing the number of animals is a requirement of the 3Rs principle. In this secondary analysis, we analyzed 28 Sprague-Dawley rats of a prospective data base that underwent 90-minute filament-occlusion of the middle cerebral artery (MCAO) to assess the predictive power of early variables at 30, 60, and 90min after occlusion. The animals were sacrificed after 72h. Infarct sizes were determined by hematoxylin staining. In a minimally invasive fashion, we recorded cerebral blood flow (CBF) with laser-Doppler flowmetry and direct current (DC)/alternating current-electrocorticography (ECoG) with epidural Ag/AgCl electrodes. Both CBF and ECoG markers correlated with the cortical infarct volumes. Multiclass receiver operating characteristic analysis identified the best predictors of three risk classes, and Spearman's rank correlation was used to explore relationships between ECoG and CBF. The slope of the CBF transients in response to spreading depolarization (SD) was the best biomarker at all time points, while the DC integral was the best epidural biomarker. Both correlated negatively at all time points (ρ < -0.68). In summary, we have found that early risk stratification during MCAO in rats is possible using minimally invasive biomarkers. This would enable, in particular, the early sorting out of animals with a low risk of cortical infarction in neuroprotection studies, where these animals typically distort the statistical results.