NEURONAL NITRIC-OXIDE SYNTHASE IS INDUCED IN SPINAL NEURONS BY TRAUMATIC INJURY

Nitric oxide appears to mediate the immune functions of macrophages, t he influence of endothelial cells on blood vessel relaxation, and also to serve as a neurotransmitter in the central and peripheral nervous system.(1,17) Macrophage nitric oxide synthase is inducible with massi ve increases in new nitric oxide synthase protein synthesis following immune stimulation of macrophages.(18) By contrast, endothelial nitric oxide synthase and neuronal nitric oxide synthase are thought to tie constitutive with activation induced by calcium entry into cells in th e absence of new protein synthesis.(4,9,15) Developmental studies show ing the transient expression of neuronal nitric oxide synthase in embr yonic and early postnatal life in rodent spinal motoneurons and cerebr al cortical plate neurons (Bredt and Snyder, unpublished observations) implies inducibility of neuronal nitric oxide synthase. Moreover, neu ronal nitric oxide synthase expression is greatly enhanced in sensory ganglia following peripheral axotomy.(8,20) Staining for NADPH diaphor ase in spinal motoneurons is greatly increased following ventral root avulsion.(22) In many parts of the Central Nervous System NADPH diapho rase staining reflects nitric oxide synthase.(3,11) In the present stu dy, we have combined in situ hybridization for neuronal nitric oxide s ynthase, immunohistochemical staining of neuronal nitric oxide synthas e, and NADPH diaphorase staining to establish that neuronal nitric oxi de synthase expression is markedly augmented in spinal motoneurons fol lowing avulsion. The generality of this effect is evident from augment ed staining in nucleus dorsalis following spinal cord transection.