Abstracts

Rationale: Glutamate excitotoxicity is a direct cause of brain injury and the accompanying changes in the electroencephalogram (EEG) after asphyxic incidents. One strategy to reduce tissue glutamate level after ischemia has emerged and involves N-acetylaspartylglutamate (NAAG) as an important storage form of glutamate. Its hydrolysis by the neuropeptidase, NAALADase, produces N-acetylaspartate (NAA) and synaptically active glutamate. The inhibition of NAALADase by 2-Phosphonomethylpentanedoic acid (2-PMPA) reduces extracellular glutamate. With the goal of developing a real-time measure of brain injury and recovery, we proceeded to test whether Q-EEG will be able to detect neuroprotective effects of 2-PMPA. We have shown in previous work that increased EEG bursting is indicative of favorable recovery and outcome post-asphyxia. In this study we use a novel EEG indicator of electrical volatility or bursting known as the residual subband wavelet entropy (RSWE).Methods: We subjected 2 groups of adult male Wistar rats(300 - 350 g) to 5 minutes of asphyxial cardiac arrest. One group was assigned to: control with vehicle (C; n=4) and the other to low dose (LD: n=5) 2-PMPA (100 mg/kg IP bolus) at 30 min before injury. EEG was monitored continuously from baseline to 4 hrs. post-return of spontaneous circulation (ROSC). Wavelet coefficients were calculated in six logarithmic bands from the super gamma (64-125 Hz) to delta (1-4 Hz). The entropies were calculated over 5 sec windows and the residual entropies were calculated for each band over individual one minute segments. The average residual entropy was calculated for each 7 minute EEG epoch and univariate t-tests taken across groups within each of these epochs.Results: For the 2-PMPA-treated group there is an increase in RSWE early after ROSC. These increases occurred in theta, alpha and gamma bands. For the theta band increases in RSWE occurred at 28, 35 & 42 min (p≤0.05) post-ROSC; for the alpha band 35 & 42 min (p≤0.04) and 42 & 49 min for the beta band (p≤0.05). Conclusions: Preliminary results indicate an increase in EEG volatility during early recovery from global asphyxia as indicated by RSWE in Naaladase-inhibitor treated animals. This volatility is most probably linked to increased bursting in the treated animals.