STUDY PF TRANSIENT EVOKED POTENTIAL

脑缺血性缺氧（HI）损伤导致氧化和 兴奋性毒性应激引起许多病理生理学和 离散的电气功能变化。我们之前的大脑研究 涉及可以通过以下方式校准损伤的大小和持续时间的方法： 使用EEG和诱发电位（EP）的电指示器。的 本提案的总体目标是评估脑电 发出信号以提供关于响应的更重要的信息 延迟性损伤应激和恢复的大脑。中央 假设是对大脑活动数学和实验评价 电信号将提供新的机制的见解， 从HI损伤中恢复的精确时间曲线， 早期康复，后期康复。 目标1将侧重于延迟损伤。大脑皮层神经电信号 进行定量评估，以确定低频的恢复， EP信号中的粗糙形状细节和EP信号的不规则恢复。 EEG的优势频率。背侧丘脑多单位记录 和网状丘脑将测试它们可能的中枢作用， 通过丘脑皮层回路开始恢复由于拖延 损伤的标志是过度的兴奋性神经递质活动， 谷氨酸释放抑制和谷氨酸转运蛋白敲低的作用 调节退行性变化的作用进行神经化学分析。 目标2将研究早期恢复。大脑皮层的信号 以EP中的高频和精细细节的回归为特征 信号以及EEG信号中的纺锤波和爆发抑制。 细胞研究将确定HI后对体感的反应， 刺激和丘脑中继神经元的梭形振荡共同作用， 与动物的恢复有关。电生理研究 躯体感觉通路和受体密度的分子操纵， 丘脑皮层回路恢复过程中的突触传递 功能将确定早期恢复的机制。目标3将 通过评估受试者的生存率和任何 在早期阶段开始治疗后的神经功能缺损。 EP和EEG信号特征的恢复将通过 结合线性和非线性建模方案。对扩展的影响 皮层和丘脑电信号的恢复将与 两种相反的操作：抑制突触谷氨酸释放 与谷氨酸转运蛋白敲除的对比。免疫化学分析将 识别导致再生变化的结构修饰， 丘脑皮质通路功能恢复良好， 躯体感觉皮层 皮质和丘脑定量分析的创新应用 信号加上新的神经化学验证的损伤和 恢复机制应导致发现基本的 电生理机制区分不同阶段的全球 HI损伤。长期的好处应该是改善诊断和新颖的 针对HI恢复各阶段的治疗策略 损伤

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.