METABOTROPIC GLU RECEPTORS IN TRAUMATIC BRAIN INJURY

说明（改编自申请人摘要）：谷氨酸盐毒性， 通过离子通道连接的受体介导的， 创伤性脑损伤（TBI）病理学和行为发病率的作用。 除了激活离子型受体，过量的谷氨酸 损伤释放的谷氨酸也激活G蛋白连接的代谢型谷氨酸 受体（mGluRs）。然而，mGLuR激活对TBI的贡献- 诱导的谷氨酸兴奋性毒性尚未系统地研究， 仍不清楚TBI诱导的mGluR cm活化理论上增加 兴奋性毒性或减少兴奋性毒性，这取决于 mGluR激活。这项研究的长期目标是 研究mGluRs影响TB的程度和机制 病理生理过程 行为、神经化学、组织学和电生理研究 将研究mGluRs在TBI病理生理学中的功能作用， 良好表征的大鼠脑损伤的液压冲击模型。通过 选择性刺激或阻断选定的受体亚型， mGluR的损伤过程、病理机制和药理作用 神经保护将使用体内微透析、受体 结合，蛋白质印迹和免疫组织化学，和功能的措施， 受体-第二信使偶联 这项研究将为谷氨酸提供新的重要见解 脑损伤中兴奋性毒性和受体介导的病理生理学 流程.这项研究还将提供临床相关信息 关于治疗人类头部疾病的潜在药物 损伤

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.