颅脑创伤后认知功能障碍是临床常见的行为障碍，与突触可塑性失调密切相关。p75NTR是神经营养因子的受体。颅脑创伤后星状胶质细胞表达增加的p75NTR是否介导突触可塑性改变而参与认知功能障碍的形成？国内外无相关报道。所以，本课题利用分子生物学、细胞生物学技术和转基因动物，从分子、细胞、脑片和整体动物等多层面，探讨颅脑创伤后星状胶质细胞的p75NTR影响突触可塑性参与认知功能障碍的机制，内容包括（1）颅脑创伤后小鼠认知功能和突触可塑性的改变、细胞存活和p75NTR的表达。（2）颅脑创伤后星状胶质细胞的p75NTR对认知功能、突触可塑性和星状胶质细胞激活和相关蛋白的影响。（3）星状胶质细胞的p75NTR影响突触可塑性的机制。本课题的完成将阐明颅脑创伤后星状胶质细胞的p75NTR影响突触可塑性参与认知功能障碍的机制，为将来针对以p75NTR为靶点的药物开发和临床改善颅脑创伤后认知功能提供新的思路。

Traumatic brain injury (TBI) results in significant cognitive deficits particularly in attention, learning and memory, and higher-order executive functions. However, despite significant effort very few therapeutic options exist to prevent or reverse cognitive impairment following TBI. Synaptic plasticity plays an important role on the cognition function. The 75 neurotrophin receptor (p75NTR, encoded by NGFR) is a transmembrane glycoprotein member of the TNF receptor (TNFR) superfamily and binds to all neurotrophins to mediate various functions. The expression of p75NTR on the astrocyte in the brain are upregulated after TBI. Whether does p75NTR expressed on the astrocyte participate cognition dysfunction via modulating synaptic plasticity after TBI? These questions remain unclear so far. Therefore, this project will explore the mechanism of p75NTR expressed on the astrocyte participating in the cognition deficient after TBI by use of molecular biology technology, cellular biology technology and transgenic animal model. The contents about this project will include three parts: (1) The determination of cognition function, synaptic plasticity, cell survival and the expression of p75NTR in the cortex and hippocampus after TBI in mice. (2) The effect of p75NTR expressed on the astrocyte on synaptic plasticity, cognition function and astrocyte reactive and related protein after TBI in mice. (3) The possible mechanism of p75NTR expressed on the astrocyte affect the cognition function and synaptic plasticity after TBI in mice. This study will help to clarify the role of p75NTR expressed on the astrocyte affecting in synaptic plasticity after TBI and highlight the contribution of p75NTR expressed on the astrocyte to the cognition dysfunction after TBI in mice. The p75NTR will provide a novel site for modifying synaptic plasticity and improving cognition after TBI, and become to be potential target for drug development in treatment TBI.