Manifestations and Outcomes of Intracerebral Hemorrhage During the COVID-19 Pandemic in China: Multicenter, Longitudinal Cohort Study.

Background: The COVID-19 pandemic has inevitably affected the distribution of medical resources, and epidemic lockdowns have had a significant impact on the nursing and treatment of patients with other acute diseases, including intracerebral hemorrhage (ICH).

Objective: This study aimed to investigate how the COVID-19 pandemic affected the manifestations and outcomes of patients with ICH.

Methods: Patients with acute ICH before (December 1, 2018-November 30, 2019) and during (December 1, 2019-November 30, 2020) the COVID-19 pandemic at 31 centers in China from the Chinese Cerebral Hemorrhage: Mechanism and Intervention (CHEERY) study were entered into the analysis.

Cell Heterogeneity Uncovered by Single-Cell RNA Sequencing Offers Potential Therapeutic Targets for Ischemic Stroke.

Ischemic stroke is a detrimental neurological disease characterized by an irreversible infarct core surrounded by an ischemic penumbra, a salvageable region of brain tissue. Unique roles of distinct brain cell subpopulations within the neurovascular unit and peripheral immune cells during ischemic stroke remain elusive due to the heterogeneity of cells in the brain. Single-cell RNA sequencing (scRNA-seq) allows for an unbiased determination of cellular heterogeneity at high-resolution and identification of cell markers, thereby unveiling the principal brain clusters within the cell-type-specific gene expression patterns as well as cell-specific subclusters and their functions in different pathways underlying ischemic stroke.

Inhibition of Sema4D/PlexinB1 signaling alleviates vascular dysfunction in diabetic retinopathy.

Diabetic retinopathy (DR) is a common complication of diabetes and leads to blindness. Anti-VEGF is a primary treatment for DR. Its therapeutic effect is limited in non- or poor responders despite frequent injections.

Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke.

Endothelium (EC) is a key component of blood-brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood.

Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke.

Angiogenesis is a crucial defense response to hypoxia that regulates the process of raising the promise of long-term neurologic recovery during the management of stroke. A high expression of antiangiogenic factors leads to the loss of neovascularization capacity in pathologic conditions. We have previously documented an impairment of the cerebral vessel perfusion and neovascularization in the cortex neighboring the stroke-induced lesion, which was accompanied by an activation of semaphorin 3E (Sema3E)/PlexinD1 after ischemic stroke.

Semaphorin-3A protects against neointimal hyperplasia after vascular injury.

Background: Neointimal hyperplasia is a prominent pathological event during in-stent restenosis. Phenotype switching of vascular smooth muscle cells (VSMCs) from a differentiated/contractile to a dedifferentiated/synthetic phenotype, accompanied by migration and proliferation of VSMCs play an important role in neointimal hyperplasia. However, the molecular mechanisms underlying phenotype switching of VSMCs have yet to be fully understood.

Acute stroke patients' knowledge of stroke at discharge in China: a cross-sectional study.

Objectives: A good mastery of stroke-related knowledge can be of great benefit in developing healthy behaviours. This study surveyed the knowledge about stroke and influencing factors among patients with acute ischaemic stroke (AIS) at discharge in a Chinese province.

Methods: A cross-section study was conducted from November 1, 2014 to January 31, 2015.

Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats.

Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signaling is involved in poststroke neovascularization remains unknown.

Sema4D/PlexinB1 inhibition ameliorates blood-brain barrier damage and improves outcome after stroke in rats.

The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear.

Alleviative effects of fluoxetine on depressive-like behaviors by epigenetic regulation of BDNF gene transcription in mouse model of post-stroke depression.

Fluoxetine, one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, has been thought to be effective for treating post-stroke depression (PSD). Recent work has shown that fluoxetine may exert an antidepressive effect through increasing the level of brain-derived neurotrophic factor (BDNF), but the underlying mechanism still remains unclear. In the present study, we successfully established the PSD model using male C57BL/6 J mice by photothrombosis of the left anterior cortex combined with isolatied-housing conditions.

MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells.

Administration of sonic hedgehog protein induces angiogenesis and has therapeutic effects after stroke in rats.

The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. Intracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7days (d).

P2Y Promotes Migration of Vascular Smooth Muscle Cells Through Cofilin Dephosphorylation During Atherogenesis.

Objective: P2Y is a well-recognized receptor expressed on platelets and the target of thienopyridine-type antiplatelet drugs. However, recent evidence suggests that P2Y expressed in vessel wall plays a role in atherogenesis, but the mechanisms remain elusive. In this study, we examined the molecular mechanisms of how vessel wall P2Y mediates vascular smooth muscle cells (VSMCs) migration and promotes the progression of atherosclerosis.

Inhibiting the Migration of M1 Microglia at Hyperacute Period Could Improve Outcome of tMCAO Rats.

Aim: To study whether inhibiting microglia migration to the ischemic boundary zone (IBZ) at the early phase could improve neurological outcomes after stroke.

Methods: The transient middle cerebral artery occlusion (tMCAO) was induced in adult male Sprague-Dawley rats. AMD3100, a highly selective CXC-chemokine receptor 4 (CXCR4) antagonist, was used to inhibit microglia migration.

MiR-181b Antagonizes Atherosclerotic Plaque Vulnerability Through Modulating Macrophage Polarization by Directly Targeting Notch1.

Atherosclerotic plaque vulnerability is the major cause for acute stroke and could be regulated by macrophage polarization. MicroRNA-181b (miR-181b) was involved in macrophage differential. Here, we explore whether miR-181b could regulate atherosclerotic plaque vulnerability by modulating macrophage polarization and the underline mechanisms.

MiR-150 Regulates Poststroke Cerebral Angiogenesis via Vascular Endothelial Growth Factor in Rats.

Aims: Angiogenesis is a harmonized target for poststroke recovery. Therefore, exploring the mechanisms involved in angiogenesis after stroke is vitally significant. In this study, we are reporting a miR-150-based mechanism underlying cerebral poststroke angiogenesis.

MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats.

The mechanism of blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-150 (miR-150)-mediated mechanism in the disruption of BBB after stroke in rats. We found that up-regulation of miR-150 increased permeability of BBB as detected by MRI after permanent middle cerebral artery occlusion in vivo as well as increased permeability of brain microvascular endothelial cells after oxygen-glucose deprivation in vitro.

CYP2C19 polymorphism and clinical outcomes among patients of different races treated with clopidogrel: A systematic review and meta-analysis.

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI).

High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH.

The development and/or progression of perihematomal edema (PHE) in patients with acute spontaneous intracerebral hemorrhage (ICH) vary substantially with different individuals. Although hematoma volume is a useful indicator for predicting PHE, its predictive power was not good at the early stage of ICH. Better predictors are urgently needed.

Endogenous endothelial progenitor cells participate in neovascularization via CXCR4/SDF-1 axis and improve outcome after stroke.

Aim: To study whether endogenous endothelial progenitor cells (EPCs) are involved in neovascularization after stroke.

Materials And Methods: Animal stroke models were established by subjecting male SD rats to permanent middle cerebral artery occlusion (pMCAO). Vessels in ischemic boundary zone (IBZ) were stained with antibody against laminin at 1 to 21 days after pMCAO.

Recombinant human sonic hedgehog protein regulates the expression of ZO-1 and occludin by activating angiopoietin-1 in stroke damage.

This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra.

Astrocyte-derived sonic hedgehog contributes to angiogenesis in brain microvascular endothelial cells via RhoA/ROCK pathway after oxygen-glucose deprivation.

The human adult brain possesses intriguing plasticity, including neurogenesis and angiogenesis, which may be mediated by the activated sonic hedgehog (Shh). By employing a coculture system, brain microvascular endothelial cells (BMECs) cocultured with astrocytes, which were incubated under oxygen-glucose deprivation (OGD) condition, we tested the hypothesis that Shh secreted by OGD-activated astrocytes promotes cerebral angiogenesis following ischemia. The results of this study demonstrated that Shh was mainly secreted by astrocytes and the secretion was significantly upregulated after OGD.