Pathophysiology of glia following traumatic brain injury

这项建议的总体目标是评估创伤后神经胶质对海马生理的影响。创伤性脑损伤（TBI）与多种神经功能缺损相关，包括记忆障碍、认知功能障碍和癫痫。 这种异常的病理生理基础仍然在很大程度上是未知的。 然而，海马兴奋性的改变似乎起着重要的作用。虽然大多数研究工作集中在神经元和突触的变化，正常的神经元功能也取决于细胞外离子浓度和细胞和细胞外体积的准确调节。 胶质细胞已被证明在细胞外体积和离子组成的稳态中，在脑组织含水量的调节中，以及在确定神经元兴奋性和功能中起关键作用。尽管神经胶质细胞具有如此重要的作用，但对TBI后神经胶质细胞急性和慢性的功能状态知之甚少。 我们建议定义TBI对海马神经胶质功能的急性和慢性影响，特别强调：1）神经胶质反应性及其电生理变化的时间模式，2）神经元和子代细胞外K+-稳态的时间模式，3）对离子和水稳态的病理生理后果，以及4）神经元和神经胶质细胞体积调节。对这些创伤后变化的研究将使TBI的治疗更加合理。

The overall goal of this proposal is to assess the impact of post-traumatic glia on hippocampal physiology. Traumatic brain injury (TBI) is associated with a wide variety of neurological deficits, including memory impairment, cognitive dysfunction and epilepsy. The pathophysiological bases of such abnormalities still remain largely unknown. However, altered hippocampal excitability appears to play an important role. While the majority of research effort focuses on neuronal and synaptic changes, normal neuronal function also depends on an accurate regulation of the extracellular ionic concentrations and cellular and extracellular volume. Glial cells have been shown to play a crucial role in the homeostasis of extracellular volume and ionic composition, in the regulation of brain tissue water content, and in determining neuronal excitability and function. In spite of such a paramount role of glia, little is known about the functional status of glial cells acutely and chronically following TBI. We propose to define the acute and chronic effects of TBI on hippocampal glial function with particular emphasis on: 1) temporal pattern of glial reactivity and their electrophysiological changes, 2) temporal pattern of neuronal and filial extracellular K+-homeostasis, 3) pathophysiological consequences on ion and water homeostasis, and 4) neuronal and glial cell volume regulation. Investigations on these post-traumatic changes will allow a more rational treatment to TBI.