Biomarker of Neuroprotectant Efficacy

描述（由申请人提供）：本I期可行性研究的目标 本研究旨在开发一种敏感的生物标记物，用于定量神经保护药物 在创伤性脑损伤（TBI）的大鼠模型中的功效。目前，没有广泛 公认的量化大鼠TBI模型中神经元损伤的生化标志物 服务器租用-美国服务租用我们以前已经证明，在轴突变性过程中， 在人类中，脑细胞骨架蛋白MAP-tau被切割。本实验室 开发了一种灵敏的ELISA，可以特异性地测量切割的MAP-tau（C-tau） 脑损伤后的脑脊液中利用这种ELISA，我们已经证明， 大鼠在持续皮质撞击诱导的TBI后C-tau水平增加。通过 通过测量病变体积，Scheff等人先前已经证明， TBI后给予环孢素A显著改善皮质 皮质撞击大鼠模型中的损伤。我们假设C-tau是一种 TBI诱导的大鼠神经元损伤的可靠生物标志物。我们将测试这个 通过确定C-tau水平是否表现出时间依赖性增加 在TBI后，如果已知的神经保护剂干预，环孢菌素A， 对C-tau水平的预期影响。我们的具体目标是： 具体目标1：确定TBI是否导致时间依赖性增加， 大脑中的C-tau蛋白水平C-tau水平将通过ELISA在TBI影响的患者中定量。 和控制大脑区域，以及假手术动物。具体目标二： 确定C-tau水平是否可靠地量化已知的 神经保护剂干预TBI。环孢素的神经保护作用 A将通过给予溶媒或环孢菌素A进行检查。C-tau 将在TBI诱导的C-tau最大时通过ELISA定量水平 具体目标1中确定的高度。将比较C-tau水平， 神经保护剂治疗的作用。

DESCRIPTION (provided by applicant): The objective of this Phase I feasibility study is to develop a sensitive biomarker for quantifying neuroprotectant drug efficacy in a rat model of traumatic brain injury (TBI). Currently, no widely accepted biochemical marker that quantifies neuronal injury in rat TBI models is available. We have previously shown that during axonal degeneration in humans, the brain cytoskeletal protein MAP-tau is cleaved. Our laboratory has developed a sensitive ELISA that specifically measures cleaved MAP-tau (C-tau) in human CSF following head injury. Using this ELISA, we have shown that brain C-tau levels increase in rats after sustaining cortical impact-induced TBI. By measuring lesion volumes, Scheff et al have previously demonstrated that cyclosporin A administration following TBI significantly ameliorates cortical damage in the cortical impact rat model. We hypothesize that C-tau is a reliable biomarker of TBI-induced neuronal injury in rats. We will test this hypothesis by determining if C-tau levels demonstrate a time-dependent increase after TBI and if a known neuroprotectant intervention, cyclosporin A, exerts expected effects on C-tau levels. Our Specific Aims are: Specific Aim 1: Determine whether TBI results in a time-dependent increase in brain levels of C-tau. C-tau levels will be quantified by ELISA in TBI-affected and control brain regions and also in sham operated animals. Specific Aim 2: Determine if C-tau levels reliably quantify the effect of a known neuroprotectant intervention on TBI. The neuroprotective effect of cyclosporin A will be examined by administering either vehicle or cyclosporin A. C-tau levels will be quantified by ELISA at the time of maximum TBI-induced C-tau elevation determined in Specific Aim 1. C-tau levels will be compared as a function of neuroprotectant treatment.