HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLO

了解BBB卒中的病理生理学至关重要，因为卒中是导致死亡和残疾的主要原因，而脑血管通透性增加是缺血性脑损伤和水肿形成的重要因素。血脑屏障开放引起的血管源性脑水肿是脑血管意外损伤后在脑内出现的一种类型的脑水肿。血管源性脑水肿可由血脑屏障处紧密连接的开放或吞噬细胞活动的增加引起。脑缺血/卒中对血脑屏障的损伤可导致卒中康复期间不良的临床结果，如血管源性脑水肿和炎症。此外，BB转运特性的改变可能会影响临床上有用的药物的转运，这些药物用于治疗缺血性发作或治疗其他疾病阶段。我们的主要假设是，低氧/血糖和再灌流(与卒中相关)改变了BB特异性蛋白的表达以及关键溶质跨血脑屏障的通透性和转运，从而促进了卒中的发展和严重程度。为了研究这一假说，我们的主要目标和具体目标是通过量化对细胞阻力、通透性、紧密连接蛋白/细胞骨架蛋白表达以及与低氧相关的特定蛋白的转录/转录后表达的影响，来研究和量化低氧/低血糖/复氧对血脑屏障内皮细胞的影响。我们还将确定钙在缺氧/血糖/复氧中的作用，并确定星形胶质细胞的作用。我们将使用的技术是体外和原位结合我们在分析生物化学和血管生物学方面的经验，在一个重点项目中研究低氧/血糖应激对血脑屏障内皮细胞的影响。

Understanding BBB stroke pathophysiology is critical since stroke is a leading cause of death and disability and increased cerebrovascular permeability is an important factor for the development of ischemic brain damage and edema formation. Vasogenic brain edema, due to a BBB opening is the type of edema that is present in the brain after injury induced by a cerebrovascular accident. Vasogenic brain edema can result from opening of tight junctions at the BBB or an increase in pinocytotic activity. Damage to the BBB from ischemia/stroke can result in poor clinical outcomes during stroke recovery, such as vasogenic brain edema and inflammation. In addition, changes in BB transport characteristics may influence the transport of clinically useful medications used to either treat the ischemic episode or medicate other disease stages. Our major hypothesis is that hypoxia/aglycemia and reperfusion (associated with stroke) alters both the expression of BB specific proteins and the permeability and transport of critical solutes across the BBB, thereby contributing to the development and severity of stroke. To investigate this hypothesis, our major objective and specific aims are to investigate and quantify the effect of hypoxia/aglycemia/reoxygenation on the endothelial cells of the BBB by quantifying effects on cell resistance, permeability, tight junctional protein/cytoskeletal protein expression and transcriptional/post-transcriptional expression of specific proteins associated with hypoxia. We will also identify the role in calcium in hypoxia/aglycemia/reoxygenation and determine the role of astrocytes. The techniques we will use are both in vitro and in situ coupling our experience of analytical biochemistry and vascular biology in a focused program to study the effect of hypoxic/aglycemic stress on endothelial cells of the BBB.