The long-term goal of this research program is to develop the t technology for evaluating and treating brain injury. Analysis of the unique elements of the brain's neuroelectric signals should produce a clear characterization of the sequence and extent of injury, and the likelihood of recovery. This study will use models of two major types of brain injury (complete focal and complete global ischemia) that are applicable to a wide range of other brain diseases. The overall strategy is to investigate brain's electrical activity in three phases of ischemia; (1) acute insult, (2) delayed excitotoxic injury, and (3) recovery and restoration of function. The specific research aims are: Phase 1: To test the hypotheses that, during the acute insult stage of ischemic injury, (a) the first changes in electrical response are a loss of high-frequency content of somatosensory evoked potentials (EP) signals, as measured by adaptive Fourier series modeling, and a decline in power of the dominant high frequencies of electroencephalogram (EEG); (b) a threshold of electrical dysfunction is reached because of failure of electrogenic pump causing a rise in extracellular potassium. Phase 2: To test the hypotheses that, during the delayed excitotoxic injury stage after the ischemic insult, (a) injury can be measured as a loss of coherence of EP signals and spectral dispersion of EEG signals; (b) the spectral measures of injury will correlate with post-mortem histological evaluation of the cortical mantle, and (c) the excitotoxic neuroelectric response and athe post-mortem histology will show improvement when brain is treatment with the glutamate antagonist MK801 or the NO- synthase inhibitor L-NAME. Phase 3: To test the hypotheses that, during the recovery stage, (a) the electrical activity is gradually restored by bursting or seizure-like EEG patterns , as measured by bispectral and bicoherence analysis of EEG; (b) the recovery of electrical function correlates with the neurologic performance of surviving animals; and (c) administration of NBQX, a AMPA/Kainate blocker, and BW1003C87, an anti-seizure drug analog, helps suppress neuronal excitability during recovery and improves the neurologic function. This research will provide new quantitative measures of EEG and EP signals referenced to physiologic events during three phases of ischemic injury postulated in this proposal. These measures will identify the neuroelectric signal parameters that are essential to improve (1) rapid clinical diagnosis of ischemic injury, (2) timing and dosing of therapeutic interventions, and (3) prediction of behavioral outcome after ischemic injury.
Showing the most recent 10 out of 53 publications
