STUDY PF TRANSIENT EVOKED POTENTIAL

缺氧缺血(HI)对脑的损伤导致氧化性和 兴奋性毒性应激，引起大量的病理生理和 离散的电功能改变。我们之前的大脑研究导致了 涉及到可以通过以下方式校准伤害的程度和持续时间的方法 使用脑电和诱发电位(EP)的电指标。这个 本提案的总体目标是评估脑电 发送信号以提供有关响应的更重要信息 大脑对迟发性损伤应激和恢复的影响。中环 假设是大脑的数学和实验评估 电子信号将提供新的机械洞察 从延迟的角度看HI损伤恢复的精确时间轮廓 受伤、早期康复、后期康复。 目标1将专注于延迟性受伤。皮质神经电信号将 进行定量评估以确定低频的恢复和 EP信号中的粗糙形状细节和不规则的恢复 脑电的主要频率。丘脑背侧的多单位记录 而网状丘脑将测试它们在 通过丘脑皮质回路启动恢复。自延迟以来 损伤的标志是兴奋性神经递质活性过高， 谷氨酸释放抑制和谷氨酸转运体基因敲除的作用 在调节退行性变化时，将用神经化学方法进行分析。 目标2将考察早期恢复情况。皮质信号将是 以EP中的高频和精细细节的回归为特征 以及脑电信号中的纺锤波和猝发抑制。 细胞研究将确定HI后对躯体感觉的反应 刺激物和丘脑中继神经元的纺锤波 动物康复的事件。电生理检查 体感通路与受体密度和受体的分子调控 丘脑皮质环路恢复过程中的突触传递 功能将定义早期恢复的机制。目标3将 通过评估受试者的存活率和任何 在早期阶段开始治疗后的神经功能障碍。 EP和EEG信号特征的恢复将通过 线性和非线性相结合的建模方案。对Extended的影响 皮质和丘脑电信号的恢复将与 两种截然不同的手法：抑制突触谷氨酸释放 与谷氨酸转运蛋白被击倒。免疫化学分析将 确定导致再生变化的结构修改，并 丘脑皮质通路功能恢复良好 躯体感觉皮质。 皮质和丘脑定量分析的创新应用 信号与损伤和新的神经化学验证相结合 恢复机制应该导致发现基本的 大脑皮层不同时相的电生理机制 嗨，受伤了。长期的好处应该是改善诊断和新奇 针对HI康复各个阶段的治疗策略 受伤。

Hypoxic ischemia (HI) injury to brain results in both oxidative and excitotoxic stresses that provoke numerous pathophysiological and discrete electrical functional changes. Our prior brain research has led to methods that can calibrate the magnitude an duration of injury by using electrical indicators of EEG and evoked potentials (EP). The overall goal of the present proposal is to evaluate cerebral electrical signaling to provide even more important information about the response of brain to delayed injury stresses as well as recovery. The central hypothesis is that mathematical and experimental evaluation of cerebral electrical signaling will provide novel mechanistic insights into the precise temporal profile of recovery from HI injury in terms of delayed injury, early recovery, and later recovery. Aim 1 will focus on delayed injury. Cortical neuroelectric signals will be quantitatively evaluated to determine recovery of low frequencies and coarse shape details in the EP signals and an irregular recovery of the dominant frequencies of EEG. Multi-unit recording in the dorsal thalamus and reticular thalamus will test their possible central role in initiating recovery via the thalamocortical circuit. Since delayed injury is marked by excess excitatory neurotransmitter activity, the role of glutamate release inhibition and glutamate transporter knockdown on modulating the degenerative changes will be assayed neurochemically. Aim 2 will examine early recovery. Cortical signals will be characterized for the return of high frequencies and fine details in EP signals as well as spindling and burst suppression in the EEG signals. Cellular studies will determine the post-HI response to somatosensory stimuli and spindle oscillations in the thalamic relay neurons co- incident with animal's recovery. Electrophysiological investigations of somatosensory pathway and molecular manipulation of receptor density and synaptic transmission during restoration of thalamocortical circuit function will define the mechanisms of early recovery. Aim 3 will explore the late recovery by evaluating the subject's survival and any neurological deficits after therapies initiated in the earlier phases. Restoration of EP and EEG signal features will be quantified by a combined linear and non-linear modeling scheme. Effects on extended recovery of cortical and thalamic electrical signals will be compared to two contrasting manipulations: inhibition of synaptic glutamate release versus glutamate transporter knockdown. Immunochemical analysis will identify structural modifications resulting in regenerative changes and good functional recovery in thalamocortical pathways and the somatosensory cortex. The innovative use of quantitative analysis of cortical and thalamic signals coupled with novel neurochemical validation of injury and recovery mechanisms should led to the discovery of basic electrophysiological mechanisms differentiating various phases of global HI injury. The long-term benefits should be improved diagnosis and novel therapeutic strategies targeted to each phase of recovery from HI injury.