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 neuronal nitric oxide synthase immunoreactivity in a rat model. Spinal cord trauma was produced by making an incision into the right dorsal horn of the T10-11 segments. Five h after trauma, a marked upregulation of NOS-immunostained neurons was seen in the perifocal T9 and T12 segments 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-induced upregulation of NOS-immunoreactivity. In contrast, application of preabsorbed serum or L-NAME, an inhibitor to NOS, was ineffective in reducing the induction of NOS-immunoreactivity. Trauma caused a marked expansion of the cord and resulted in marked cell changes. This expansion and cell reaction was significantly reduced following application of NOS antiserum but it was not seen after application of preabsorbed antiserum or L-NAME. Our results for the first time show that a focal trauma to the spinal cord has the capacity to upregulate neuronal NOS immunoreactivity and that application of NOS antiserum has a neuro protective effect. This indicates that nitric oxide is somehow involved in the pathogenesis of secondary injuries after spinal cord trauma.