HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLO

了解BBB卒中病理生理学至关重要，因为卒中是死亡和残疾的主要原因，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。血管源性脑水肿，由于血脑屏障开放，是脑血管意外引起的损伤后存在于脑中的水肿类型。血管源性脑水肿可由BBB处的紧密连接的开放或胞饮活性的增加引起。缺血/卒中对BBB的损伤可导致卒中恢复期间的不良临床结局，例如血管源性脑水肿和炎症。此外，BB转运特性的变化可能影响用于治疗缺血发作或预防其他疾病阶段的临床有用药物的转运。我们的主要假设是，缺氧/无糖血症和再灌注（与中风相关）改变了BB特异性蛋白质的表达和关键溶质穿过BBB的渗透性和转运，从而导致中风的发展和严重程度。为了研究这一假设，我们的主要目的和具体目标是通过量化对细胞阻力、渗透性、紧密连接蛋白/细胞骨架蛋白表达以及与缺氧相关的特定蛋白的转录/转录后表达的影响，来研究和量化缺氧/血糖缺乏/复氧对BBB内皮细胞的影响。我们还将确定钙在缺氧/无糖/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在体外和原位耦合我们的分析生物化学和血管生物学的经验，在一个集中的计划，以研究缺氧/无糖皮质激素应激对BBB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.