METABOTROPIC GLU RECEPTORS IN TRAUMATIC BRAIN INJURY

描述(摘自申请者摘要)：谷氨酸毒性， 通过离子通道连接的受体介导的一个成熟的关键 在创伤性脑损伤(TBI)病理和行为发病中的作用。 除了激活亲离子受体外，过量的谷氨酸 损伤释放也激活G蛋白连接的代谢性谷氨酸 受体(MGluRs)。然而，mGluR激活对脑损伤的贡献- 诱导的谷氨酸兴奋性毒性还没有得到系统的研究 目前仍不清楚。脑损伤后mGluR-cm的激活在理论上增加 兴奋性毒性或降低兴奋性毒性取决于 MGluR已激活。这项研究的长期目标是 调查mGluRs影响结核病的程度和机制 病理生理过程。 行为、神经化学、组织学和电生理学研究 将研究mGluRs在脑损伤病理生理学中的功能作用 在大鼠脑损伤模型上建立了具有良好特征的流体冲击模型。通过 选择性地刺激或阻断选定的受体亚型 MGluR损伤过程、机制及药理学研究 神经保护将使用体内微透析受体进行检查 结合、免疫印迹和免疫组织化学及功能测定 受体-第二信使偶联。 这项研究将为谷氨酸提供新的和重要的见解 脑损伤的兴奋性毒性与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。 关于治疗人头疾病的潜在药理药物 受伤。

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.