INVOLVEMENT OF NITRIC-OXIDE IN ACUTE SPINAL-CORD INJURY - AN IMMUNOCYTOCHEMICAL STUDY USING LIGHT AND ELECTRON-MICROSCOPY IN THE RAT

The possibility that nitric oxide participates in the pathophysiology of spinal cord injury was examined using a constitutive isoform of neu ronal nitric oxide synthase immunoreactivity in a rat model. Spinal co rd trauma was produced by making an incision into the right dorsal hor n of the T10-11 segments. Five h after trauma, a marked upregulation o f NOS-immunostained neurons was seen in the perifocal T9 and T12 segme nts of the cord. The immunolabelling was most pronounced in the dorsal horn of the ipsilateral side. Topical application of an antiserum to nitric oxide synthase (NOS) 2 min after injury prevented the trauma-in duced upregulation of NOS-immunoreactivity. In contrast, application o f preadsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the induction of NOS-immunoreactivity. Trauma caused a marke d expansion of the cord and resulted in marked cell changes. This expa nsion and cell reaction was significantly reduced following applicatio n of NOS antiserum but it was not seen after application of preadsorbe d antiserum or L-NAME. Our results for the first time show that a foca l trauma to the spinal cord has the capacity to upregulate neuronal NO S immunoreactivity and that application of NOS antiserum has a neuropr otective effect. This indicates that nitric oxide is somehow involved in the pathogenesis of secondary injuries after spinal cord trauma.