认知功能损害是蛛网膜下腔出血(SAH)患者常见后遗症之一，其机制目前仍不清楚。高剂量谷氨酸刺激可导致细胞骨架肌动蛋白与其调控蛋白cofilin异常形成栓状结构（rod），阻碍神经元胞浆运输，损害突触以及突触传递和可塑性。我们前期研究已显示SAH可引起海马区谷氨酸的大量积聚。因此，我们提出如下假说：SAH导致海马区谷氨酸大量释放诱导cofilin rod在海马神经元中形成，导致神经元突触丢失、突触传递以及可塑性等损害，进而引起行为学上的认知功能损害。本项目将应用行为学检测、免疫组化、电生理等技术，1）探讨SAH是否导致海马区cofilin rod的形成而损伤海马神经元突触形成和突触可塑性，2） 阐明SAH诱导谷氨酸异常大量释放是引起rod生成的主要因素。本项目旨在证实SAH诱导cofilin rod生成导致认知功能损害的新理论，为SAH引起脑损伤和认知功能损害的治疗提供新的有效治疗途径。

Cognitive dysfunction is one of the long-term complications in majority patients suffer with subarachnoid hemorrhage (SAH). However, its underline mechanism remains unclear. Actin and cofilin, a cytoskeletal actin modulator, could form rods (called cofilin rod) under certain abnormal condition such as glutamate excitotoxic stimulation. Rods in dendrits block intracellular trafficking and induce loss of synapse and impairment of synaptic plasticity. Our previous study has demonstrated that SAH induces large amount of glutamate accumulation in hippocampus. Therefore, we hypothesis that excitotoxic glutamate stimulation during SAH induces cofilin and actin to form rod structure which in turn triggering the loss of synapse and the impairment of synaptic transmission and plasticity, and further induced cognitive dysfunction. By applying behavioral, immunohistochmistry and electrophysiological techniques, we will reveal 1) whether SAH will trigger the cofilin rod formation and in turn causes synaptic loss and impairment cognition, and 2) whether large amount of glutamate accumulation in the hippocampus is the cause of the cofilin rod formation. From this study, we try to reveal a new mechanism underline SAH related cognitive dysfunction and provide new theory for treatment.