In vivo damage of CNS myelin and axons induced by peroxynitrite

In multiple sclerosis (MS) the mechanisms of injury caused by peroxynitrite remain uncertain. To study histological, ultra structural and molecular al terations caused by peroxynitrite in brain, the peroxynitrite donor 3-morph olinosydnonimine was injected in rat corpus callosum. Peroxynitrite, induce s strong primary axonal damage with characteristics of primary acute axonop athy, together with severe myelin alteration, myelin vacuolation and demyel ination, and nitrotyrosine formation as confirmed by detection of nitrosate d target proteins. Administration of the peroxynitrite, scavenger uric acid inhibited these effects. In vivo, peroxynitrite leads to a disorganisation of myelin and to axonal damage presenting, some similarities to the format ion of MS lesions. Understanding the action of peroxynitrite, in this proce ss will open new therapeutic strategies by specific inhibition of peroxynit rite. formation and action. (C) 2001 Lippincott Williams & Wilkins.