新生儿缺氧缺血性脑病（HIE）是儿童难治疾病，亟需探索其修复策略。缺氧缺血(HI)引起的脑血管功能障碍是导致HIE的重要原因。周细胞是构成脑血管的关键细胞,对脑血管功能维持至关重要。研究发现，HI时周细胞大量死亡，导致严重的脑血管功能障碍。因而，阐明HI后周细胞死亡的确切机制，维持其存活，可望减轻脑血管功能障碍，进而改善脑功能。前期细胞实验中，我们发现Parthanatos抑制剂优于其它死亡通路抑制剂，能最大程度抑制HI诱导的周细胞死亡，且HI后周细胞表现出典型的Parthanatos分子特征，提示Parthanatos是HI后周细胞死亡的主要途径。本研究将建立体外培养脑周细胞氧糖剥夺模型和新生大鼠缺氧缺血脑损伤模型，阐明Parthanatos在HI后脑周细胞死亡中的作用和分子机制，探讨Parthanatos抑制策略改善HI后脑血管功能障碍的可行性与最佳作用时间窗，为HIE治疗提供新思路。

Neonatal hypoxic-ischemic encephalopathy (HIE) is a severe disease of nervous system. It is very important to explore the reparation mechanism of HIE. Hypoxia-ischemia (HI) induced dysfunction of brain vessels is the key factor contributing to the development and progression of brain damage. Pericytes are present at intervals along the walls of capillaries, constituting the main components of brain blood vessels. In the central nervous system, they are important for the maintenance of the function of blood vessels. Recent studies revealed that pericyte death is a rapid response of the cerebral vascular bed to ischemia, which is the key factor that contributes to the dysfunction of brain vessels. Therefore, elucidating the exact mechanisms contributing to pericyte death will be beneficial for the identification of appropriate strategies to maintain pericyte survival, and thus attenuate HI-induced dysfunction of brain vessels. In our preliminary work, we found that parthanatos inhibitor protects against HI-induced cell-death better than other inhibitors of other modes of cell-death in cultured pericytes. The biochemical features of parthanatos, PARP1activation, poly-ADP ribose (PAR) up-regulation, and AIF translocation from cytoplasm to nucleus were evident in HI-exposed pericytes, suggesting that parthanatos might be the primary death mode of pericytes subjected to HI. In the present study, using oxygen-glucose deprivation of cultured pericytes and a Vannuci HI brain damage rat model, we’ll try to elucidate the exact role and mechanism of parthanatos in pericyte death induced by HI, explore the feasibility and the best time window of using parthanatos inhibitory strategy to ameliorate blood vessel dysfunction induced by HI, thus provide new ideal for HIE therapy.