Ketamine promotes hippocampal CA1 pyramidal neuron loss after a short-duration ischemic insult in rats

The neuroprotective activity of the N-methyl-D-aspartate (NMDA) antagonist ketamine was examined in two groups of rats subjected to forebrain ischemia of differing durations. Ketamine provided a limited degree of protection against hippocampal CA1 pyramidal cell loss following a 10 min ischemic insult. In contrast after 6 min ischemia, which in non-treated control animals resulted in less CA1 neuron loss than was seen after 10 min ischemia, ketamine at the same dose worsened outcome. The data indicate that the possession by a drug of NMDA antagonist activity does not alone determine its neuroprotective activity in vivo.