缺血性中風導致患者腦神經死亡與神經功能障礙，因此預防缺血性中風所造成的神經死亡為目前關鍵治療研究之一。腦中除了神經細胞之外，更多的是神經膠細胞，包括：微膠細胞與星狀膠細胞，研究證實微膠細胞與星狀膠細胞在中風後的神經死亡扮演重要的角色，但其中的機制目前仍有許多不清楚。過去的研究發現，缺血性中風導致神經死亡透過的途徑有細胞凋亡與細胞壞死，至今，有更多的死亡途徑被發現，包括：細胞程序性壞死、細胞焦亡與細胞自噬，然而這些死亡途徑在缺血性中風後的神經細胞、微膠細胞與星狀膠細胞中扮演的角色仍未釐清，因此，本研究主要探討缺血性中風後的神經細胞、微膠細胞與星狀膠細胞之死亡途徑，及微膠細胞與星狀膠細胞在神經死亡中扮演的角色。本研究利用缺氧缺糖或缺氧處理神經細胞 (N18)、微膠細胞 (BV-2)與星狀膠細胞 (C6)，來模擬活體動物發生缺血性中風的現象。首先觀察到在缺血性中風處理下，神經細胞與微膠細胞，相較星狀膠細胞，細胞增生情形顯著下降，且細胞內Cleaved-caspase-3蛋白與RIP1蛋白表現量顯著上升，Caspase-1活性顯著上升，培養基中乳酸脫氫酶顯著增加，表示細胞凋亡、細胞程序性壞死、細胞焦亡與壞死被活化，而在星狀膠細胞中則無觀察到此現象。細胞自噬則在缺血性中風後的神經細胞、微膠細胞與星狀膠細胞都有被活化，但神經細胞與星狀膠細胞內的自噬體與溶酶體無結合，導致自噬體堆積。而缺血性中風早期，活化細胞自噬有助於細胞存活，在晚期，抑制細胞自噬則有助於細胞存活，但若是溶酶體的功能缺失，不論早期或晚期皆造成細胞死亡。最後發現缺氧缺糖處理的微膠細胞條件培養基有助於神經細胞增生，進一步發現隨缺氧缺糖處理，微膠細胞M1型態之基因表現 (il-1, cd86)逐漸下降，而M2型態之基因表現 (arg-1)則顯著上升，且與神經細胞共培養下，增加神經細胞內自噬體形成。本研究結論：缺血性中風造成神經細胞與微膠細胞死亡，透過活化細胞凋亡、細胞程序性壞死、細胞焦亡與壞死等途徑，而細胞自噬則隨中風時間增加對細胞有不同的影響，早期有助於細胞存活，後期則會造成存活下降。其中發現缺氧缺糖的微膠細胞有助於神經細胞的存活，透過M2型態的轉換及早期活化神經細胞自噬。

Ischemic stroke is one of the critical brain injuries that cause neuronal death and neurological deficit in patients. The microglia and astrocytes could play an important role in ischemic stroke. However, the underlying mechanisms of microglia and astrocytes in the neuronal consequences after ischemic stroke have not been thoroughly investigated. In the present study, we aimed to identify the cell fate of microglia and astrocyte, their contribution to ischemic stroke-induced neuronal consequence, and identify potential mediators in these processes. Neurons, microglia and astrocytes cell lines (N18, BV-2, and C6, respectively) were treated with oxygen-glucose deprivation (OGD) or hypoxia serving as an in vitro model of ischemic stroke. The microglia and neurons, rather than astrocytes were more vulnerable to ischemic condition. The apoptosis, necrosis, necroptosis, pyroptosis were elicited in ischemic neurons and microglia, but not in astrocytes. Autophagy were elicited in and played an important role in ischemic neurons, microglia and astrocytes. Finally, the ischemic microglia promoted neuronal survival by transform of M2 type and activation of neuronal autophagy.

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