Urethane anesthesia produces selective damage in the piriform cortex of the developing brain

The potential induction of neuronal death by neuroactive drugs at specific stages of embryonic or postnatal development is a serious concern in treati ng brain disease. Recent evidence indicates that NMDA antagonists, GABA ago nists, ethanol and some anesthetics can all produce massive neuronal cell l oss at critical times during development. We show here that the anesthetic urethane, once used clinically, produces a selective lesion of the piriform cortex, a region not previously implicated in such toxicity, in the develo ping brain. Young rats were injected with urethane at 1, 2, 3, and 4 weeks of age and brain damage was measured 1-4 days later. We found that urethane produces a large lesion in subfields of the piriform cortex and that the d amage is most severe in 2 week-old animals. These data, together with other recent reports, show that there are multiple neuronal death-inducing pathw ays in the developing nervous system. It will be important to determine if anesthesties used in pregnant women and young children may have similar eff ects. (C) 2001 Elsevier Science B.V. All rights reserved.