Pathophysiology of glia following traumatic brain injury

这项建议的总体目标是评估创伤后胶质细胞对海马区生理的影响。创伤性脑损伤与多种神经功能障碍有关，包括记忆障碍、认知功能障碍和癫痫。这种异常的病理生理学基础在很大程度上仍不清楚。然而，海马区兴奋性的改变似乎起到了重要作用。虽然大部分研究工作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对细胞外离子浓度和细胞外体积的准确调节。神经胶质细胞在维持细胞外体积和离子组成的动态平衡、调节脑组织水分含量、决定神经元兴奋性和功能等方面发挥着至关重要的作用。尽管胶质细胞发挥着如此重要的作用，但对脑外伤后神经胶质细胞的急性和慢性功能状态知之甚少。我们建议定义脑损伤对海马区神经胶质功能的急性和慢性影响，特别强调：1)神经胶质细胞反应性的时间模式及其电生理变化，2)神经元和子代细胞外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的体积调节。对这些创伤后变化的研究将有助于更合理地治疗颅脑损伤。

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.