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.
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| D'Ambrosio, Raimondo; Fairbanks, Jared P; Fender, Jason S et al. (2004) Post-traumatic epilepsy following fluid percussion injury in the rat. Brain 127:304-14 |
