The amount of messenger RNA encoding human inducible nitric oxide synt
hase and the presence and distribution of NADPH diaphorase were determ
ined in tissue sections from multiple sclerosis (MS) and control brain
s. Levels of human nitric oxide synthase messenger RNA were markedly e
levated in MS brains when compared to normal control brains. NADPH dia
phorase activity, a histochemical stain reflecting nitric oxide syntha
se catalytic activity, was detected in reactive astrocytes in active d
emyelinating MS lesions and at the edge of chronic active demyelinatin
g lesions. Control brains did not contain NADPH diaphorase-positive as
trocytes. These results implicate the free radical nitric oxide in the
pathogenesis of demyelinating MS lesions.