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.

Cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie-infected mice.

The presence of cytokines, prostaglandins and lipocortin-1 was investigated in terminally affected mice in two models of scrapie. There was marked induction of glial interleukin-1 beta, tumour necrosis factor alpha, prostaglandin E2, prostaglandin F2 alpha and lipocortin-1 immunoreactivity in those areas of the brain showing the characteristic vacuolation of scrapie. A comparison of these staining patterns with those of GFAP and F4/80 showed that their expression occurred predominantly in astrocytes. It is possible that cytokines play a significant role in the pathogenesis of neurodegeneration in scrapie.

Immunocytochemical detection of prostaglandin E2 in microvasculature and in neurons of rat brain after administration of bacterial endotoxin.

The aim of the present study was to identify the site of prostaglandin E2 (PGE2) production in the brain in response to a pyrogenic dose of endotoxin. The presence of PGE2 was detected using immunocytochemistry on Bouin's fixed vibratome sections of control and endotoxin-treated rats. Peripheral administration of endotoxin caused a time-related stimulation of PGE2 immunoreactivity (irPGE2) in the choroid plexus and in the microvasculature of the brain. In addition to these sites, hypophysiotrophic neurons of the paraventricular nucleus (PVN) and supraopticus nucleus (SON) responded with induction of irPGE2 to endotoxin administration. Our data demonstrate that alterations in brain function in response to endotoxin may involve arachidonic metabolites such as PGE2 that are induced at the blood-brain barrier (microvasculature) and blood-liquor barrier (choroid plexus) and in hypophysiotrophic neurons of the rat brain.