METABOTROPIC GLU RECEPTORS IN TRAUMATIC BRAIN INJURY

描述（改编自申请人摘要）：谷氨酸毒性，

DESCRIPTION (Adapted from Applicant's Abstract): Glutamate toxicity, mediated via ion channel-linked receptor plays a well established, key role in traumatic brain injury (TBI) pathology and behavioral morbidity. In addition to activation of ionotropic receptors, excessive glutamate released by injury also activates G-protein-linked, metabotropic glutamate receptors (mGluRs). However, the contribution of mGLuR activation on TBI- induced glutamate excitotoxicity has not been systematically examined and remains unclear. TBI-induced activation of mGluR cm theoretically increase excitotoxicity or decrease excitotoxicity depending upon the subtype of mGluR activated. The long term objectives of this research are to investigate the extent of, and the mechanisms by which mGluRs influence TB pathophysiological processes. Behavioral, neurochemical, histological, and electrophysiological studies will examine the functional role of mGluRs in TBI pathophysiology using a well characterized, fluid percussion model of brain injury in the rat. By selectively stimulating or blocking selected subtypes of receptors during the injury process, mechanisms of mGluR pathology and pharmacological neuroprotection will be examined using in vivo microdialysis, receptor binding, western blot and immunohistochemistry, and functional measures of receptor-second messenger coupling. This research will provide new and important insights into glutamate excitotoxicity and receptor mediated pathophysiology in brain injury processes. This research will also provide clinically relevant information about potential pharmacological agents for the treatment of human head injury.