Consequences of Cardiac Arrest: Brain Injury

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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.