Translational Stroke Research最新文献

To investigate the association between rs402007 polymorphism in the ADAMTS-1 gene and carotid atherosclerotic plaque vulnerability, as well as the lipid-lowering efficacy of atorvastatin in cerebral infarction patients. Clinical data from 684 cerebral infarction patients admitted to The First Hospital of Hebei Medical University (2016-2019) were analyzed. Patients were stratified into stable plaque (n = 338) and vulnerable plaque (n = 346) groups based on carotid ultrasound. General information, biochemical markers, rs402007 (G/C) genotypes (dominant model), and allele frequencies were compared. Polymorphism genotyping was performed using TaqMan SNP assays (Applied Biosystems) on an ABI 7500 Fast Real-Time PCR system. Logistic regression evaluated plaque vulnerability risk factors and gene-risk factor interactions. Atorvastatin's lipid-lowering efficacy was compared across genotypes. Diabetes prevalence, LDL-C, TC, HCY, and FIB levels differed significantly between groups (P < 0.05). Genotypic distribution analysis revealed a higher frequency of the GG genotype in the stable plaque group (29.59% vs. 21.68%, χ² = 5.618, P = 0.018). Diabetes, LDL-C, HCY, and FIB were independent risk factors for plaque vulnerability (P < 0.05). A significant interaction between rs402007 polymorphism and LDL-C was observed (P < 0.05). Atorvastatin efficacy rates were 82.29% (GG), 84.27% (GC), and 89.27% (CC), with significant post-treatment lipid improvements in all genotypes (P < 0.05). The CC genotype exhibited superior efficacy compared to GG (P < 0.05). The rs402007 polymorphism influences carotid plaque vulnerability and modulates atorvastatin efficacy, underscoring its potential role in genotype-guided therapeutic strategies.

Electroencephalogram (EEG) during pinprick stimulation has the potential to unveil neural mechanisms underlying sensorimotor impairments post-stroke. A proof-of-concept study explored event-related peak pinprick amplitude and oscillatory responses in healthy controls and in people with acute and subuacute motor and sensorimotor stroke, their relationship, and to what extent EEG somatosensory responses can predict sensorimotor impairment. In this study, 26 individuals participated, 10 people with an acute and early subacute sensorimotor stroke, 6 people with an acute and early subacute motor stroke, and 10 age-matched controls. Pinpricks were applied to the dorsa of the impaired hand to collect somatosensory evoked potentials. Time(-frequency) analyses of somatosensory evoked potential (SEP) data at electrodes C3 and C4 explored peak pinprick amplitude and oscillatory responses across the three groups. Also, in stroke, (sensori-)motor impairments were assessed with the Fugl Meyer Assessment Upper Extremity (FMA) and Erasmus modified Nottingham Sensory Assessment (EmNSA) at baseline and 7 to 14 days later. Mixed model analyses were used to address objectives. It was demonstrated that increased beta desynchronization magnitude correlated with milder motor impairments (R²_adjusted = 0.213), whereas increased beta resynchronization and delta power were associated to milder somatosensory impairment (R²_adjusted = 0.550). At the second session, larger peak-to-peak SEP amplitude and beta band resynchronization at baseline were related to greater improvements in EMNSA and FMA scores, respectively, in the sensorimotor stroke group. These findings highlight the potential of EEG combined with somatosensory stimuli to differentiate between sensorimotor and motor impairments in stroke, offering preliminary insights into both diagnostic and prognostic aspects of upper limb recovery.

The rupture of vulnerable plaques is the principal cause of luminal thrombosis in acute ischemic stroke. The identification of plaque features that indicate risk for disruption may predict cerebrovascular events. Here, we aimed to build a high-risk intracranial plaque model that differentiates symptomatic from asymptomatic plaques using radiomic features based on high-resolution magnetic resonance imaging (HRMRI). One hundred and seventy-two patients with 188 intracranial atherosclerotic plaques (100 symptomatic and 88 asymptomatic) with available HRMRI data were recruited. Clinical characteristics and conventional plaque features on HRMRI were measured, including high signal on T1-weighted images (HST1), the degree of stenosis, normalized wall index, remodeling index, and enhancement ratio (ER). Univariate and multivariate analyses were performed to build a traditional model to differentiate between symptomatic and asymptomatic plaques. Radiomic features were extracted from pre-contrast and post-contrast HRMRI. A radiomic model based on HRMRI was constructed using random forests, ridge, least absolute shrinkage and selection operator, and deep learning (DL). A MIX model was constructed based on the radiomic model and the traditional model. Gender, HST1, and ER were associated with symptomatic plaques and were included in the traditional model, which had an area under the curve (AUC) of 0.697 in the training set and 0.704 in the test set. The radiomic model achieved an AUC of 0.982 in the training set and 0.867 in the test dataset for identifying symptomatic plaques. In the training set, the MIX model showed an AUC of 0.977. In the test set, the MIX model exhibited an improved AUC of 0.895, which outperformed the traditional model (p = 0.032). Radiomic analysis based on DL and machine learning can accurately identify high-risk intracranial plaques.

To evaluate whether endovascular thrombectomy (EVT) combined with best medical management (BMM) is more effective than BMM alone in treating mild stroke patients (National Institutes of Health Stroke Scale score < 6) with large vessel occlusion (LVO). A multicentric retrospective cohort of patients with LVO and mild stroke within 24 h from symptom onset was included. Patients were divided into the primary EVT (EVT_pri) group and the primary BMM (BMM_pri) group according to the treatment strategy. Functional outcomes were compared after propensity score matching. Additionally, adjusted logistic regression analysis was used to assess the association between treatment strategy and functional outcomes. Finally, 419 patients were included, with 137 receiving EVT_pri and 282 receiving BMM_pri. After propensity score matching (EVT_pri, 126 vs. BMM_pri, 126), baseline characteristics were balanced between the two groups. No significant difference was observed in 3-month functional independence (modified Rankin Scale [mRS] 0-2, 78.6% vs. 76.2%. In the overall cohort, EVT_pri was not associated with functional independence (adjusted odds ratio [aOR], 0.87; 95% confidence interval [CI], 0.43-1.47). However, patients in the EVT_pri group were more likely to experience symptomatic intracranial hemorrhage (aOR, 1.27; 95% CI, 1.05-1.89). Subgroup analysis revealed that EVT_pri was significantly associated with functional independence in vertebrobasilar occlusion subgroup (aOR, 1.78; 95% CI, 1.20-3.90). Our findings did not support the systematic use of EVT for mild stroke with LVO, except in cases of vertebrobasilar occlusion, which may represent a subgroup where EVT_pri could provide significant benefits.

Ischemic stroke often leads to neurological deficits, including olfactory dysfunction, which can significantly diminish quality of life. Photobiomodulation (PBM) has emerged as a promising therapeutic strategy for enhancing post-stroke recovery, although the molecular mechanisms, particularly regarding gene expression change, are not yet fully understood. This study investigates the long-term effects of photothrombosis (PT) on olfactory function and the olfactory bulb (OB) microenvironment, with a focus on PBM's efficacy during both early and late phases. In a mouse OB PT stroke model, PBM therapy (808-nm laser, 40 J/cm² fluence, 325 mW/cm², 2 min daily) was applied from day 2 to day 7 post-PT. Olfactory function was monitored from pre-stroke through day 28 using the buried food test (BFT), and MRI scans were performed on days 7 and 28 to assess tissue damage. RNA sequencing (RNA-seq) and reverse transcription quantitative PCR (RT-qPCR) were conducted on day 7 to evaluate gene expression changes, with additional RT-qPCR analyses performed on day 28. PBM significantly accelerated olfactory function recovery by day 14, with full recovery maintained through day 28. Despite functional recovery, MRI results indicated persistent infarction at 28 days. RNA-seq identified upregulation of neuroprotective genes, including Gpr39 and Or4m1, following PBM treatment, suggesting enhanced gene expression related to acute-phase recovery. However, the impact of PBM on gene expression and functional recovery appeared to wane in the later stages of recovery. These findings underscore PBM's potential to enhance early-stage recovery in ischemic stroke, though its benefits may be more limited in the chronic phase.

Spontaneous intracranial artery dissection (sIAD) is the leading cause of stroke in young individuals. Identifying high-risk sIAD cases that exhibit symptoms and are likely to progress is crucial for treatment decision-making. This study aimed to develop a model relying on circulating biomarkers to discriminate symptomatic sIADs. The study prospectively collected sIAD tissues and corresponding serums from January 2020 to December 2022 as the discovery cohort. Symptomatic sIADs were defined as those with mass effect, hemorrhagic, or ischemic stroke. A stratification model was developed using the machine-learning algorithm within the derivation cohort (a cross-sectional cohort including from January 2018 to August 2022) and validated within the validation cohort (a longitudinal cohort including from January 2017 to April 2023). In the discovery cohort (n = 10, 5 symptomatic), analyses of tissues and serums revealed 15 proteins and 2 cytokines with significance between symptomatic and asymptomatic sIADs. Among these biomarkers, six proteins and one cytokine, participating in the immune response and inflammatory-related pathways, have a good consistency in expression level between sIAD tissues and serums. In the derivation cohort (n = 181, 77 symptomatic), a model incorporating these 7 biomarkers was highly discriminative of symptomatic sIADs (area under curve [AUC], 0.95). This model performed well in predicting the occurrence of sIAD-related symptoms in the validation cohort (n = 84, 26 symptomatic) with an AUC of 0.88. This study revealed seven circulating biomarkers of symptomatic sIAD and provided a high-accuracy model relying on these circulating biomarkers to identify symptomatic sIADs, which may aid in clinical decision-making for sIADs.

Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.

Stereotactic radiosurgery (SRS) is a non-invasive treatment option for brain arteriovenous malformations (bAVMs). However, SRS cures are delayed, making it less favorable for higher risk ruptured bAVMs (rbAVMs) than unruptured (ubAVMs). This systematic review and meta-analysis explores the long-term outcomes of SRS-focused protocols for rbAVMs and ubAVMs. This study adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Literature search was conducted using PubMed, Ovid Medline, Scopus, and hand-search on January 30th, 2025. The inclusion criteria encompassed studies: distinguishing cohorts by rupture status, reporting post-SRS outcomes, and without overlapping series. Pooled analysis was performed from 24 articles using DerSimonian-Laird random effects models. Subgroup and meta-regression analyses were also conducted. All analyses were performed using R. For rbAVMs, the pooled rupture, obliteration, and mortality rates were 7.14% (95% CI: 5.76%-8.64%), 65.0% (95% CI: 57.2%-72.4%), and 0.87% (95% CI: 0.00%-5.14%), respectively, and for ubAVMs, 6.13% (95% CI: 4.71%-7.69%), 59.5% (95% CI: 51.3%-67.3%), and 0.89% (95% CI: 0.00%-3.82%), respectively. Subgroup meta-analyses of rupture rates and obliteration rates showed no significant differences based on prior treatments (Q = 2.47, p = 0.48; Q = 4.34, p = 0.23; respectively) or volume-staging protocols (Q = 4.90, p = 0.18; Q = 1.12, p = 0.77, respectively). Meta-regression analysis for rbAVMs demonstrated a positive correlation between intranidal aneurysms and rupture rate (p < 0.05, R² = 100%), an inverse correlation between Spetzler-Martin (SM) grade I-II bAVMs and obliteration rate (p < 0.05, R² = 68.6%), and a positive correlation between SM grade III-V bAVMs and obliteration rate (p < 0.05, R² = 68.0%). Meta-regression analysis for ubAVMs demonstrated an inverse correlation between eloquent-region lesions and rupture rate (p < 0.05, R² = 31.3%), and surprisingly a positive correlation between mean age and obliteration rate (p < 0.05, R² = 23.8%). SRS-focused studies show similar long-term outcomes regardless of rupture status, but presence of underlying factors indicates the need for individualized risk-benefit analysis.

Ischemic stroke disrupts protein homeostasis in brain cells, causes endoplasmic reticulum (ER) stress, and consequently activates the unfolded protein response (UPR). The primary function of UPR activation is to help cells restore ER function, thereby promoting cell survival. A major adaptive UPR branch is mediated by activating transcription factor 6 (ATF6). We previously provided experimental evidence that activation of ATF6 signaling in neurons improves short-term outcome after both transient and permanent stroke. However, the effect of ATF6 activation in astrocytes on stroke outcome remains undetermined, and critically, the long-term therapeutic potential of targeting this UPR branch in permanent stroke has not been evaluated. The current study aimed to address these two critical unknowns. First, using conditional knock-in mice in which functional short-form ATF6 (sATF6) is specifically expressed in astrocytes, we demonstrated that astrocytic ATF6 activation modestly improved outcome after permanent stroke. Then, our pharmacokinetic analysis indicated that compound AA147, an ATF6-specific activator, can cross the blood-brain barrier. Lastly, we found that post-stroke treatment with AA147 had no significant beneficial effect on short-term outcome, but improved long-term functional recovery in both young and aged mice after permanent stroke. Together with previous findings, our data support the notion that the ATF6 pathway is a promising target for stroke therapy.