Neuronal NOS deficiency promotes apoptotic cell death of spinal cord neurons after peripheral nerve transection.

To study the role of endogenous NO in survival and recovery of spinal cord neurons after nerve lesions, wild type mice were compared to knock-out mice lacking neuronal, endothelial or inducible NO synthase (NOS) after sciatic nerve transection. The NO-generating capacities were assessed by NOS immunohistochemistry and NADPH-diaphorase staining. The feature of affected neurons was evaluated following Nissl- and TUNEL-staining, by immunocytochemical demonstration of cytochrome c-translocation, and by ultrastructural examination. Time point of cell loss was found to be independent of the mice type and occurred only at later post-axotomy states. The extent of neuronal degeneration, however, depended on the NO supply. Whereas a lack of endothelial or inducible NOS was well tolerated, deficiency of neuronal NOS enhanced the competence-to-die and led to a substantial apoptotic cell death of spinal cord neurons. Thus, NO supply turned out to be essential for cell survival and recovery with reference to the neuronal NOS isoform. Copyright 2004 Elsevier Inc.