Appearance of inducible nitric oxide synthase in the rat central nervous system after rabies virus infection and during experimental allergic encephalomyelitis but not after peripheral administration of endotoxin.

The cellular localization of inducible (iNOS) and constitutive (cNOS) nitric oxide synthase was studied in rats by immunocytochemical techniques involving specific iNOS and cNOS directed antibodies and by NADPH-diaphorase histochemistry. Paraformaldehyde-fixed vibratome sections of brains and cryostat sections of peripheral lymph nodes were studied of rats treated with endotoxin (2.5 micrograms/kg or 2.5 mg/kg i.v.), rats infected with rabies virus, and rats exposed to experimental allergic encephalomyelitis (EAE). Endotoxin-treated animals showed no appearance of immunoreactive iNOS (ir-iNOS) cells in the brain with the exception of a few microglial cells near the median eminence and some meningeal macrophages. In the same animals however, iNOS-immunoreactive cells were found in peripheral lymph nodes. Neurons that stain positive for cNOS and for NADPH-diaphorase could be observed in brains of control as well as of endotoxin-treated animals with a similar distribution and staining intensity. In contrast, animals that had been infected with rabies virus or subjected to EAE, showed the appearance of ir-iNOS-positive cells in several brain areas. These cells are located near blood vessels and lesion sites. The majority of these cells are GSA-I-B4 isolectin-positive and therefore are likely to represent macrophages. Our data suggest that increased production of nitric oxide may play a role in the altered brain functions in rabies-infected and EAE rats. On the contrary, increased nitric oxide production is probably not involved in the non-specific symptoms of sickness induced by endotoxin.