Nellgård et al.  designed a randomized study to evaluate histologic outcome in rats subjected to different durations of severe forebrain ischemia and to explore the anesthetic neuroprotection of halothane versus  isoflurane. Sixty Sprague-Dawley rats were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane and 60% N2O or with 0.75 MAC halothane and 60% N2O. Rats in the isoflurane group were subjected to either 6.5 or 8.0 min of ischemia, and rats in the halothane group endured 6.5 min of ischemia. Four days later, histologic damage was assessed. The forebrains of rats in the isoflurane group with 6.5 min of ischemia had fewer dead hippocampal CA1 neurons compared with those found in the rats in the halothane group. However, the increase in the ischemic interval to 8 min in isoflurane-anesthetized rats resulted in the same amount of neuronal necrosis as was found in the halothane-anesthetized rat group. Although they provided evidence that cerebral metabolic rate reduction can have a beneficial effect on outcome of severe brain ischemia, the results also suggest that such benefit is small.