Pathophysiology of glia following traumatic brain injury

本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）与多种神经功能缺陷有关，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在很大程度上仍然未知。然而，海马兴奋性的改变似乎起着重要作用。虽然大多数研究都集中在神经元和突触的变化上，但正常的神经元功能也依赖于细胞外离子浓度和细胞内外体积的准确调节。神经胶质细胞已被证明在细胞外体积和离子组成的稳态、脑组织含水量的调节以及决定神经元的兴奋性和功能方面起着至关重要的作用。尽管神经胶质细胞的作用如此重要，但对于脑外伤后神经胶质细胞的急性和慢性功能状态知之甚少。我们建议定义脑外伤对海马神经胶质功能的急性和慢性影响，特别强调：1)神经胶质反应性的时间模式及其电生理变化，2)神经元和子细胞外K+稳态的时间模式，3)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调查将使创伤性脑损伤得到更合理的治疗。

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.