缺血性脑梗死再通治疗常伴随再灌注损伤会加重神经细胞死亡，其病理机制尚不完全清楚，也没有理想的干预方法。脑糖原是中枢神经系统重要能源物质。我们前期实验发现脑梗死再通患者以及脑缺血再灌注恒河猴和小鼠的星形胶质细胞出现明显的糖原累积。通过筛查糖原合成和糖原分解代谢通路关键酶的表达和活性，发现星形胶质细胞糖原分解代谢限速酶——脑型糖原磷酸化酶（PYGB）的表达和活性显著降低。因此，我们推测星形胶质细胞在脑缺血再灌注过程中出现了糖原分解代谢异常和累积，不能给周围神经元快捷供能，神经元只能利用自身葡萄糖有氧氧化供能并产生大量的氧自由基，加重神经元损伤。本课题拟运用生物化学和神经生物学等方法研究脑缺血再灌注过程中脑糖原代谢重塑规律，阐明星形胶质细胞糖原累积对自身和周围神经元活性和功能的影响，揭示再灌注损伤的发病机制，观察靶向干预PYGB对再灌注损伤的减轻作用，为缺血性脑梗死的再通治疗提供新的策略。

Reperfusion injury is associated with recanalization therapy in ischemic stroke, which may aggravate neuronal cell death. However, the pathophysiological mechanisms of cerebral ischemia-reperfusion injury are still largely unknown. And at present, there are no effective interventions. Brain glycogen is the critical energy substance in the central nervous system. We previously found a remarkable glycogen accumulation in the astrocytes of patients with cerebral infarction recanalization and cerebral ischemia-reperfusion models in rhesus monkeys and mice. In addition, by screening the expression and activity of key enzymes in glycogen synthesis and glycogenolysis, we found significantly decreased expression and activity of brain glycogen phosphorylase (PYGB), a rate-limiting enzyme in glycogenolysis. Therefore, we hypothesized that there were blocked glycogen glycogenolysis and accumulated glycogen in astrocytes during the process of cerebral ischemia and reperfusion. Subsequently, astrocytes could not quickly fuel to the surrounding neurons. Instead, neurons could only use their own glucose which entering aerobic oxidation to provide energy and generate a large number of oxygen free radicals, aggravating the damage of neurons. By using the methods of biochemistry and neurobiology, this project aimed to study the characteristics of glycogen metabolism in cerebral ischemia-reperfusion, clarify the effects of astrocytic glycogen accumulation to the functions of itself and the surrounding neurons, reveal the pathogenesis of reperfusion injury, observe the therapeutic effect by targeting PYGB in reperfusion, provide new strategies for recanalization in ischemic stroke.