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Isoflurane anesthesia alters the brains electroencephalograhical response to ischemia: EEG parameters associated with high-grade CA1 neuronal injury following global cerebral ischemia in the rat

Li-Xian Li, Kym Campbell, Shiguang Zhao, Neville W. Knuckey and Bruno P. Meloni

This study reports our re-assessment of the rat 2-vessel occlusion plus hypotension model using isoflurane (in N2O/O2). To identify the animals that developed high-grade CA1 injury (<10% neuronal survival) following 8-minutes carotid occlusion plus hypotension of 37 mmHg, we observed electroencephalogram (EEG) recordings and CA1 neuronal survival rates of 60 ischemic rats. In addition, in a neuroprotective trial, we treated ischemic rats with mild hypothermia (35°C/24h) and magnesium (IV: loading dose 360 μmol/kg; 48h infusion 120 μmol/kg/h) commencing 2 hours post-ischemia. Assessed 7 days after ischemia, the mean percentage of CA1 neuronal survival rate of the 60 rats was 12.6 ± 15.2% (mean ± SD). EEG recovery times of >14 minutes and ≤12 minutes consistently resulted in CA1 neuronal survival rates of <10% and >10%, respectively. Animals that recorded an isoelectric EEG and recovered their EEG activity between >12 minutes to 14 minutes post-ischemia, also developed high-grade CA1 injury; the reliability of these parameters was confirmed in a prospec-tive trial. Finally, hypothermia/magnesium treatment increased CA1 neuronal survival from 7.9 ± 0.9% to 55.3 ± 11.6%. By classifying EEG patterns during and post-ischemia we can identify (by surgery completion) animals that will develop high-grade CA1 injury. We also demonstrated that neuroprotection was achievable in our model.