FUNCTIONAL IMPAIRMENT AND RECOVERY AFTER FLUID PERCUSSION BRAIN INJURY

我们建议研究大脑功能障碍的机制。 创伤性脑损伤(TBI)后并阐明康复过程 这可能是治疗干预的目标。在本文的第1部分中 项目中，我们建议将体外神经生理学技术 使用认知神经行为评估来评估时间进程 创伤后海马区抑制回路的改变 选择性空间和运动异常的海马区的文献证据 细胞放电。认知关系的强弱 行为和这些指标的海马回路功能障碍将 阐明海马体在产生功能缺陷中的作用 与脑挫伤的相关性以及海马区重组是否起作用 为功能恢复干杯。在第二部分，我们将调查TBI的影响 海马长时程增强与长时程增强的关系 (LTD)，用海马片制备。提出了实验方案。 这将决定脑损伤是否诱导NMDA受体的过度激活 海马区介导LTP的抑制以及NMDA受体是否 在体外过度激活将模拟脑损伤诱导的LTP抑制。部分地 3，我们将使用新开发的三维放射自显影 联合表达局部葡萄糖利用的图像平均法 通过激活体感回路来定量定位区域 脑损伤后的电路重组。这些功能数据将是 辅以免疫细胞化学和原位杂交研究 评估突触前和突触后标志物和基因的局部变化 与电路重构相关的表达。最后，慢慢地发展 丘脑退行性变将作为治疗的靶向使用 碱性成纤维细胞生长因子对躯体感觉的保护作用 电路结构和功能。总而言之，这些研究应该有助于 有关神经系统对脑创伤AS反应的新信息 以及澄清可能针对的恢复机制 治疗性干预。

We propose to investigate the mechanisms underlying brain dysfunction following traumatic brain injury (TBI) and to clarify recovery processes that may be targeted for therapeutic intervention. In Part 1 of this project, we propose to combine in vitro neurophysiological techniques with cognitive neurobehavioral assessment to evaluate the temporal course of alterations in hippocampal inhibitory circuitry after trauma and to document evidence for aberrant spatial and movement selective hippocampal cellular discharge. The strength of the relationship between cognitive behavior and these indices of hippocampal circuit dysfunction will clarify the role of the hippocampus in generating the functional deficits associated with TBI and whether hippocampal reorganization contributes to functional recovery. In Part 2, we will investigate the effects of TBI on hippocampal long-term potentiation (LTP) and long-term depression (LTD), using the hippocampal slice preparation. Experiments are proposed that will determine whether TBI-induced over activation of NMDA receptors in hippocampus mediates the suppression of LTP and whether NMDA receptor overactivation in vitro will mimic TBI-induced LTP suppression. In Part 3, we will use a newly developed three-dimensional autoradiographic imaging averaging method of expressing local glucose utilization combined with somatosensory circuit activation to quantitatively pinpoint areas of circuit reorganization after TBI. These functional data will be complemented by immunocytochemical and in situ hybridization studies to assess local alterations in pre- and postsynaptic markers and gene expression associated with circuit remodeling. Finally, slowly developing thalamic retrograde degeneration will be targeted for treatment using basic fibroblast growth factor in an attempt to protect somatosensory circuit structure and function. Together, these studies should contribute new information concerning the response of the nervous system to TBI as well as clarifying recovery mechanisms that may be targeted for therapeutic intervention.