Neuroprotective and neurodestructive functions of nitric oxide after spinal cord hemisection

Nitric oxide (NO) may subserve different functions in different central neu rons subjected to axotomy The difference may depend on whether the neurons basally express neuronal nitric oxide synthase (nNOS), a biosynthetic enzym e of NO. This is supported by our previous finding that suggests the differ ential role of NO in neurons of nucleus dorsalis (ND) and red nucleus (RN) which have different basal expression of nNOS. This study aimed to establis h firmly the functions of NO, as revealed by nNOS immunoreactivity and nico tinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry , by the administration of endogenous NO donor, L-arginine (L-arg), and NOS inhibitor, L-N-G-nitroarginine methyl ester (L-NAME). To relate the role o f NO to glutamate receptors (GluR), the distributions of alpha-amino-3-hydr oxy-5-methl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspar tate receptor (NMDAR) in the two nuclei were revealed by immunohistochemica l techniques. nNOS immunoreactivity was void in ND neurons, but expressed w eakly in the RN normally It was induced in ipsilateral ND neurons and upreg ulated on both sides of RN after spinal cord hemisection. Neuronal loss in the ipsilateral ND was augmented by L-arg, but reduced by L-NAME. In the co ntralateral RN, L-arg attenuated neuronal loss. NMDAR1 was present in most neurons in ND, After axotomy some NMDAR1 immunoreactive neurons of the ipsi lateral ND were induced to express NOS, whereas RN neurons showed strong st aining for NMDAR1 and all the AMPA subunits. Most of the NOS-positive neuro ns in the RN were coexistent with GluR2 in normal rats and those subjected to axotomy. The present data demonstrated that NO exerted neurodestructive function in the non-NOS-containing ND neurons characterized by NMDAR as the predominant glutamate receptor. NO might be beneficial to the NOS-containi ng RN neurons. This could be attributed to the presence of GluR2. Possible diverse synthesizing pathways of NO in two different central nuclei were su ggested from the observation that NOS was colocalized with NADPH-d in ND ne urons, but not in RN neurons. (C) 2000 Academic Press.