FUNCTIONAL IMPAIRMENT AND RECOVERY AFTER FLUID PERCUSSION BRAIN INJURY

我们建议研究脑功能障碍的潜在机制 创伤性脑损伤（TBI）后，并澄清恢复过程 可以作为治疗干预的目标。 在第1部分中， 项目中，我们建议将体外神经生理学技术与联合收割机 用认知神经行为评估来评估时间进程 创伤后海马抑制回路的改变， 记录了空间和运动选择性海马异常的证据 细胞放电认知与认知之间关系的强度 行为和海马回路功能障碍的这些指标将 阐明海马在产生功能缺陷中的作用 以及海马重组是否有助于 功能恢复。在第2部分中，我们将研究TBI的影响 海马长时程增强（LTP）和长时程抑郁 (LTD)采用海马脑片制备。实验提出了 这将决定TBI是否诱导了NMDA受体的过度激活， 在海马介导的抑制LTP和是否NMDA受体 体外过度活化将模拟TBI诱导的LTP抑制。部分 3、我们将采用新开发的三维放射自显影 表示局部葡萄糖利用的成像平均方法 通过激活躯体感觉回路， 脑外伤后的电路重组这些功能数据将 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记物和基因的局部改变 与电路重构相关的表达。最后，慢慢发展 丘脑退行性变性将有针对性的治疗， 碱性成纤维细胞生长因子，试图保护躯体感觉 电路结构和功能。总之，这些研究应该有助于 关于神经系统对TBI的反应的新信息， 并澄清可能针对以下方面的恢复机制： 治疗干预

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.