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 after neonatal facial nerve transection. In situ DNA fragmentation labelling showed that axotomized motoneurons die by an apoptotic mechanism. In order to investigate the existence of excitotoxic mechanisms in this 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) were found to be able to rescue motoneurons from cell death induced by axotomy. The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester was also able to protect motoneurons from death, but to a lesser extent. The distribution of constitutive and inducible isoforms of nitric oxide synthase was investigated by immunocytochemistry in the facial motor nucleus. No changes were detected in constitutive nitric oxide synthase immunoreactivity in the facial motor nucleus after axotomy. However, in the axotomized facial motor nucleus, inducible nitric oxide synthase showed a positive immunolabelling specifically located in activated astrocytes, but not in microglia. Nitric oxide derived from activated astrocytes may have a role in promoting excitotoxic mechanisms in axotomized motoneurons. We conclude that excitotoxic mechanisms involving apoptotic cell death are present when immature motoneurons die as a consequence of target disconnection.
Casanovas
A
A
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Catalonia, Spain.
Ribera
J
J
Hukkanen
M
M
Riveros-Moreno
V
V
Esquerda
J E
JE
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001369:Axons / Q000502:physiology; D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000032:analysis; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005154:Facial Nerve / Q000473:pathology; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D000077213:Lamotrigine; D009046:Motor Neurons / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D014227:Triazines / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D014227:Triazines; D016291:Dizocilpine Maleate; D004247:DNA; D006735:Horseradish Peroxidase; D019001:Nitric Oxide Synthase; D002118:Calcium; D000077213:Lamotrigine; D019331:NG-Nitroarginine Methyl Ester