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Background Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro. Methods and results Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CTexo), mild hypoxia astrocytes (O2R24exo) which were applied oxygen-glucose deprivation for 2 h and reperfusion for 24 h (OGD2hR24h) and severe hypoxia astrocytes (O4R24exo) which were applied oxygen-glucose deprivation for 4 h and reperfusion for 24 h (OGD4hR24h). Exosomes (20 µg/ml) were co-cultured with OPCs for 24 h and their proliferation, differentiation and migration were detected. The results showed that AS-Exo under severe hypoxia (O4R24exo) inhibit the proliferation of OPCs. Meanwhile, all exosomes from three groups can promote OPCs differentiation and migration. Compared to control, the expressions of MAG and MBP, markers of mature oligodendrocytes, were significantly increased in AS-Exo treatment groups. AS-Exo treatment significantly increased chemotaxis for OPCs. Conclusions AS-Exo improve OPCs' differentiation and migration, whereas AS-Exo with severe hypoxic precondition suppress OPCs' proliferation. AS-Exo may be a potential therapeutic target for myelin regeneration and repair in white matter injury or other demyelination related diseases.

Objective—Intracerebral hemorrhage (ICH) is the second most common subtype of stroke with higher mortality and morbidity, and it lacks effective 6-month prognostic markers,especially in young patients.The aim of this research is to construct a newly valuable prognostic nomogram model incorporating hemoglobin level for young patients with ICH.Method—Patients aged between 18 and 50 years with first-ever intracerebral hemorrhageselected from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January1,2012 to December 31,2018.We retrospectively analyzed 565 young patients with ICH. The independent factors of prognosis were identified by univariate and multivariate logistic regression analysis. Then，based on independent risk factors,a new nomogram model was further constructed and validated. Its clinical value was subsequently explored utilizing decision curve analysis and clinical impact curve.Results—A total of 565 patients were enrolled in this study.There were 117 patients (20.7%) who developed unfavourable prognosis. Infratentorial lesion(adjusted odds ratio [aOR]=3.708,95%confidence interval [CI],1.490-9.227; P=0.005)was most significant with unfavourable outcome.Age([aOR]=1.054;95%CI,1.014-1.096;P=0.008),hematoma volume(aOR=1.014,95%CI,1.002-1.027;P=0.024),hemoglobin(aOR=0.981,95% CI,0.969-0.993;P=0.002),blood glucose(aOR=1.135,95%CI,1.037-1.241; P=0.005)and NIHSS(aOR=1.105,95%CI,1.069-1.141;PConclusion—The hemoglobin level at admission may be an easily overlooked factor in clinical work.This new nnomogram model could be a promising and convient tool to predict the early functional prognosis of in young people with ICH.In addition, more prospective multicenter studies are needed to cestimate these findings.

The white matter hyperintensity (WMH) multispot pattern, as multiple punctate subcortical foci, could differentiate cerebral amyloid angiopathy (CAA) from hypertensive arteriolopathy. Nevertheless, the pathophysiology underlying the multispot sign is still inexplicit. We aimed to explore risk factors for multispot patterns in cerebral small vessel disease (CSVD)-related intracerebral hemorrhage (ICH). Between June 2018 and January 2020, we retrospectively rated the WMH multispot pattern while blinded to our prospective spontaneous ICH cohort's clinical data. Demographic, genetic, and neuroimaging characteristics were applied in establishing the multispot pattern models via multiple logistic regression. In total, 268 participants were selected from our cohort. The possession of apolipoprotein E (APOE) ε2 (P = 0.051) was associated with multispot WMH in univariate analysis. Multispot WMHs were accompanied by multiple CAA features, such as centrum semiovale (CSO)-perivascular space (PVS) predominance (P = 0.032) and severe CSO-PVS (P 0.001). After adjusting for confounding factors, APOE ε2 possession (OR 2.99, 95% CI [1.07, 8.40]; P = 0.037), severe CSO-PVS (OR 2.39, 95% CI [1.09, 5.26]; P = 0.031), and large posterior subcortical patches (P = 0.001) were independently correlated with the multispot pattern in multivariate analysis. Moreover, APOE ε2 possession (OR 4.34, 95% CI [1.20, 15.62]; P = 0.025) and severe CSO-PVS (OR 3.39, 95% CI [1.23, 9.34]; P = 0.018) remained statistically significant among the participants older than 55 years of age and with categorizable CSVD. APOE ε2 and severe CSO-PVS contribute to the presence of WMH multispot patterns. Because the multispot pattern is a potential diagnostic biomarker in CAA, genetics-driven effects shed light on its underlying vasculopathy. Clinical Trial Registration: URL- http://www.chictr.org.cn . Unique identifier: ChiCTR-ROC-2000039365. Registration date 2020/10/24 (retrospectively registered).

Vascular cognitive impairment is the second most common cause of dementia which can be induced by chronic cerebral hypoperfusion. Regulatory T cells (Tregs) have been proven to provide beneficial effects in several central nervous system (CNS) diseases, but the roles of Tregs in chronic cerebral hypoperfusion-induced white matter damage have not been explored. In this study, Foxp3-diphtheria toxin receptor (DTR) mice treated with diphtheria toxin (DT) and wild type C57BL/6 mice treated with anti-CD25 antibody were subjected to bilateral carotid artery stenosis (BCAS). Flow cytometry analysis showed Tregs were widely distributed in spleen whereas barely distributed in brain under normal conditions. The distribution of lymphocytes and Tregs did not change significantly in spleen and brain after BCAS. Depletion of Tregs decreased the numbers of mature oligodendrocytes and anti-inflammatory microglia at 14 days and 28 days following BCAS. And pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interferon-γ (IFN-γ) showed higher expression after Tregs depletion. In contrast, Tregs depletion did not change the overall severity of white matter injury as shown by the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), luxol fast blue (LFB) staining and electron microscopy assay. Moreover, Tregs depletion had marginal effect on cognition defects after BCAS revealed by Morris water maze and novel object recognition examination at 28 days after BCAS. In summary, our results suggest an anti-inflammatory role of Tregs with marginal effects on white matter damage in mice after BCAS-induced chronic cerebral hypoperfusion.

BACKGROUND SMASH-U is a systematic aetiological classification system for intracerebral haemorrhage (ICH) proven to be a predictor of post-ICH haematoma expansion and mortality. However, its role in predicting functional outcome remains elusive. Therefore, we aimed to investigate whether SMASH-U is associated with long-term functional outcome after ICH and improves the accuracy of prediction when added to max-ICH score. METHODS Consecutive acute ICH patients from 2012 to 2018 from the neurology department of Tongji Hospital were enrolled. ICH aetiology was classified according to the SMASH-U system. The association of SMASH-U with 12-month functional outcome after ICH and the predictive value were evaluated. RESULTS Of 1938 ICH patients, the aetiology of 1295 (66.8%) patients were classified as hypertension, followed by amyloid angiopathy (n = 250, 12.9%), undetermined (n = 159, 8.2%), structural lesions (n = 149, 7.7%), systemic disease (n = 74, 3.8%) and medication (n = 11, 0.6%). The baseline characteristics were different among the six aetiologies. In multivariate analysis, SMASH-U was proven to be a predictor of 12-month unfavourable functional outcome. When adding the SMASH-U system, the predictive performance of max-ICH score was improved (area under the receiver operating characteristic curve from 0.802 to 0.812, p = 0.010) and the predictive accuracy was enhanced (integrated discrimination improvement [IDI]: 1.60%, p

Background Seizure is a common clinical manifestation of cerebral venous thrombosis (CVT). The mortality rate of patients with CVT with seizure is three times higher than that of patients without seizure. The aim of this study was to develop a nomogram to predict the individual probability of acute seizure events in patients with CVT. Method This was a single-center, retrospective cohort study. We analyzed and compared demographic variables, epidemiological risk factors, clinical presentation, laboratory results and imaging data in a cohort of 142 patients who were diagnosed with CVT in our hospital from January 2013 to December 2018. A nomogram was constructed to predict the risk of early seizure (ES) in these patients according to the multivariable logistic regression analysis results. The concordance index, GiViTi calibration belt and decision curve analysis (DCA) were used to assess nomogram performance. Results Forty-three (30.28%) patients experienced seizure within 2 weeks after a CVT diagnosis. Multivariate analysis identified focal neurologic deficit, Glasgow Coma Scale (GCS) scores ≤8 on admission, hemorrhagic lesions, superior sagittal sinus thrombosis (SSST) and frontal lobe lesions as independent predictive factors for ES occurrence after CVT. A nomogram was generated based on these predictive factors with the concordance index reaching 0.82, indicating that the clinical tool was well calibrated. DCA showed that the model was useful with a threshold probability in the range of 0% to 77%. Conclusions We developed the first nomogram that could predict the risk of ES in CVT patients. This effective and convenient tool has shown promising clinical benefit and will assist clinicians in making treatment decisions.

Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE.A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data.A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p = 0.020), but not APOE ε4 copies (p 0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p 0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p 0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p = 0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p = 0.026) but not in deep ICH (p 0.2). No significant association was found between APOE ε4 copies and either lobar (p 0.2) or deep ICH (p 0.2).The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.

Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage to the brain tissue. Therefore, treatment for oxidative stress is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but the clinical studies have not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used to deliver drugs and have demonstrated excellent performance in treating various diseases. Additionally, some nanomaterials have shown potential in scavenging reactive oxygen species (ROS) in stroke according to the nature of nanomaterials. The drugs’ delivery ability of nanomaterials has great significance for the clinical translation and application of antioxidants. It increases drug blood concentration and half-life and targets the ischemic brain to protect cells from oxidative stress-induced death. This review summarizes the characteristics and progress of nanomaterials in the application of antioxidant therapy in stroke, including ischemic stroke, hemorrhagic stroke, and neural regeneration. We also discuss the prospect of nanomaterials for the treatment of oxidative stress in stroke and the challenges in their application, such as the toxicity and the off-target effects of nanomaterials.

Stroke is a neurological disease responsible for significant morbidity and disability worldwide. However, there remains a dearth of effective therapies. The failure of many therapies for stroke in clinical trials has promoted the development of human cell-based models, such as brain organoids. Brain organoids differ from pluripotent stem cells in that they recapitulate various key features of the human central nervous system (CNS) in three-dimensional (3D) space. Recent studies have demonstrated that brain organoids could serve as a new platform to study various neurological diseases. However, there are several limitations, such as the scarcity of glia and vasculature in organoids, which are important for studying stroke. Herein, we have summarized the application of brain organoid technology in stroke research, such as for modeling and transplantation purposes. We also discuss methods to overcome the limitations of brain organoid technology, as well as future prospects for its application in stroke research. Although there are many difficulties and challenges associated with brain organoid technology, it is clear that this approach will play a critical role in the future exploration of stroke treatment.

Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro.Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CTAS-Exo improve OPCs' differentiation and migration, whereas AS-Exo with severe hypoxic precondition suppress OPCs' proliferation. AS-Exo may be a potential therapeutic target for myelin regeneration and repair in white matter injury or other demyelination related diseases.

Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH.