PREVENTION BY LAMOTRIGINE, MK-801 AND N-OMEGA-NITRO-L-ARGININE METHYL-ESTER OF MOTONEURON CELL-DEATH AFTER NEONATAL AXOTOMY

Motoneuron cell death was analysed in the rat facial motor nucleus aft er neonatal facial nerve transection. In situ DNA fragmentation labell ing showed that axotomized motoneurons die by an apoptotic mechanism. In order to investigate the existence of excitotoxic mechanisms in thi s type of neuronal death, rats were treated with several agents known to possess neuroprotective action through a variety of mechanisms. The Na+ channel inhibitor lamotrigine and the antagonist for the N-methyl -D-aspartate-type glutamate receptor, dizocilpine maleate (MK-801) wer e found to be able to rescue motoneurons from cell death induced by ax otomy. The nitric oxide synthase inhibitor N-omega-nitro-L-arginine me thyl ester was also able to protect motoneurons from death, but to a l esser extent. The distribution of constitutive and inducible isoforms of nitric oxide synthase was investigated by immunocytochemistry in th e facial motor nucleus. No changes were detected in constitutive nitri c oxide synthase immunoreactivity in the facial motor nucleus after ax otomy. However, in the axotomized facial motor nucleus, inducible nitr ic oxide synthase showed a positive immunolabelling specifically locat ed in activated astrocytes, but not in microglia. Nitric oxide derived from activated astrocytes may have a role in promoting excitotoxic me chanisms in axotomized motoneurons. We conclude that excitotoxic mecha nisms involving apoptotic cell death are present when immature motoneu rons die as a consequence of target disconnection.