Consequences of Cardiac Arrest: Brain Injury

描述（由申请人提供）： 心脏骤停（CA）后电和化学事件的病理生理级联反应通常会导致死亡。在幸存者中，脑损伤是发病的主要原因。不幸的是，CA后的中枢神经系统功能的调查一直受到限制的连续可观察的参数来量化和跟踪损伤。我们已经发现了这样的标志物，使用定量脑电图（Q-EEG）分析在啮齿动物模型的全脑缺血性脑损伤。使用这种标记物，我们第一次能够滴定脑损伤，监测恢复过程，并研究损伤和恢复的电生理和生化机制。我们提出了三个主要目标：1）损伤滴定：我们将开发和利用两个新的Q-EEG参数。倒频谱距离用于量化与损伤相关的高频功率损失，熵分析用于识别EEG中指示恢复阶段爆发的同步性。2)电生理学机制”记录皮层和丘脑中的神经元尖峰活动，从而确定恢复期间观察到的高频EEG和爆发的起源。3)生化机制：探讨联合调节兴奋性（谷氨酸）和抑制性（GABA）神经递质对促进电生理恢复的益处。我们将测试我们的电生理参数的灵敏度，以检测恢复过程的增强。这项工作的创新之处在于开发了新的定量工具来表征大脑对损伤的反应。意义在于这些工具的应用，研究电生理恢复，特别是有关的保护抑制系统同时控制兴奋性过度刺激。通过将损伤的机制和严重程度与定量电参数联系起来，我们的方法将产生在实验室和临床上有用的新工具。这些方法的实施将开辟新的治疗方法，以促进CA后受损大脑的恢复。

DESCRIPTION (provided by applicant): The pathophysiological cascade of electrical and chemical events following cardiac arrest (CA) often results in death. Among the survivors, brain injury is the leading cause of morbidity. Unfortunately, investigations of central nervous system function following CA have been limited by the unavailability of continuously observable parameters to quantify and track injury. We have discovered such markers using quantitative EEG (Q-EEG) analysis in a rodent model of global ischemic brain injury. Using this marker, for the first time, we are able to titrate the brain injury, monitor the recovery process, and study the electrophysiological and biochemical mechanisms of injury and recovery. We propose three major goals: 1) Injury titration: We will develop and utilize two novel Q-EEG parameters. Cepstral Distance to quantify the loss of high-frequency power associated with injury, and Entropy Analysis to identify synchrony in the EEG indicative of bursting during the recovery phase. 2) Electrophysiological mechanisms" To record neuronal spike activity in the cortex and thalamus thus identifying the origins of high-frequency EEG and bursting seen during recovery. 3) Biochemical mechanisms: To investigate the benefits of combined modulation of excitatory (glutamate) and inhibitory (GABA) neurotransmitters to promote electrophysiologic recovery. We will test the sensitivity of our electrophysiologic parameters to detect enhancement of the recovery process. The innovation of this work lies in the development of novel quantitative tools for characterizing the brain's response to injury. The significance lies in the application of these tools to study electrophysiologic recovery, particularly as related to the preservation of inhibitory system concurrent with the control of excitatory overstimulation. By linking the mechanism and severity of injury to quantitative electrical parameters, our approach will result in novel tools useful in the lab and clinic. Implementation of these methods will open new therapeutic approaches to enhance recovery of the injured brain after CA.