circDLGAP4对缺血性脑卒中后星形胶质细胞异质性的调控及其机制研究

Ischemic Stroke is a cerebrovascular disease that can cause severe damage to the brain and in turn negatively impacting its ability to function or even causing death. Neuroinflammation has been shown to play an important role in pathological injury after Ischemic Stroke. Astrocytes are glial cells found in the brain and spinal cord have been implicated in neuroinflammation. Our previous studies have indicated that circDLGAP4 is downregulated in the plasma of Acute Ischemic Stroke patients and in ipsilateral astrocytes from the brains of mice subjected to ischemic challenge. Upregulation of circDLGAP4 expression significantly attenuated neurological deficits and decreased infarct areas in the mouse stroke model. Therefore, we hypothesize that circDLGAP4 is involved in regulation of astrocyte heterogeneity after Ischemic Stroke. This proposal is both novel and innovative in that the efficacy of circDLGAP4 over-expression in abrogating the dysfunction of astrocytes can be of value for stroke-mediated neuroinflammation. Our study will help clarify the role of circDLGAP4 in regulating neuroinflammation after Ischemic Stroke and provide insight into the development of innovative therapies.

缺血性脑卒中是一种发病率、死亡率和致残率极高的常见急性脑血管病，对人类生命和健康造成严重威胁。神经炎性反应在缺血性脑卒中发生后的病理损伤中起着重要作用，哺乳动物脑内分布最为广泛的星形胶质细胞在神经炎性反应中扮演重要角色。前期研究结果表明，急性缺血性脑卒中患者血浆中circDLGAP4，以及缺血性脑卒中模型鼠梗死侧星形胶质细胞内circDLGAP4的表达水平均显著下降。此外，过表达circDLGAP4可以有效改善缺血性脑卒中症状，减小梗死体积。因此，申请者提出“circDLGAP4调控星形胶质细胞异质性治疗缺血性脑卒中”这一假设，验证circDLGAP4的治疗作用及其细胞分子机制，并确定星形胶质细胞不同功能状态下的关键调控分子和标志物，为缺血性脑卒中的客观诊断和治疗提供新思路。

缺血性脑卒中是一种发病率、死亡率和致残率极高的常见急性脑血管病，对人类生命和健康造成严重威胁。神经炎性反应在缺血性脑卒中发生后的病理损伤中起着重要作用，哺乳动物脑内分布最为广泛的星形胶质细胞在神经炎性反应中扮演重要角色。前期研究结果表明，急性缺血性脑卒中患者血浆中circDLGAP4，以及缺血性脑卒中模型鼠梗死侧星形胶质细胞内circDLGAP4的表达水平均显著下降。此外，过表达circDLGAP4可以有效改善缺血性脑卒中症状，减小梗死体积。因此，申请者提出“circDLGAP4调控星形胶质细胞异质性治疗缺血性脑卒中”这一假设，验证circDLGAP4的治疗作用及其细胞分子机制，并确定星形胶质细胞不同功能状态下的关键调控分子和标志物，为缺血性脑卒中的客观诊断和治疗提供新思路。