Early and late neuropathological features of meningoencephalitis associated with Maraba virus infection

Maraba virus is a member of the genus Vesiculovirus of the Rhabdoviridae family that was isolated in 1983 from sandflies captured in the municipality of Maraba, state of Pará, Amazônia, Brazil. Despite 30 years having passed since its isolation, little is known about the neuropathology induced by the Maraba virus. Accordingly, in this study the histopathological features, inflammatory glial changes, cytokine concentrations, and nitric oxide activity in the encephalon of adult mice subjected to Maraba virus nostril infection were evaluated. The results showed that 6 days after intranasal inoculation, severe neuropathological-associated disease signs appeared, including edema, necrosis and pyknosis of neurons, generalized congestion of encephalic vessels, and intra- and perivascular meningeal lymphocytic infiltrates in several brain regions. Immunolabeling of viral antigens was observed in almost all central nervous system (CNS) areas and this was associated with intense microglial activation and astrogliosis. Compared to control animals, infected mice showed significant increases in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (INF)-γ, MCP-1, nitric oxide, and encephalic cytokine levels. We suggest that an exacerbated inflammatory response in several regions of the CNS of adult BALB/c mice might be responsible for their deaths.

NADPH-diaphorase activity in area 17 on the squirrel monkey visual cortex: neuropil pattern, cell morphology and laminar distribution

We studied the distribution of NADPH-diaphorase activity in the visual cortex of normal adult New World monkeys (Saimiri sciureus) using the malic enzyme "indirect" method. NADPH-diaphorase neuropil activity had a heterogeneous distribution. In coronal sections, it had a clear laminar pattern that was coincident with Nissl-stained layers. In tangential sections, we observed blobs in supragranular layers of V1 and stripes throughout the entire V2. We quantified and compared the tangential distribution of NADPH-diaphorase and cytochrome oxidade blobs in adjacent sections of the supragramular layers of V1. Although their spatial distributions were rather similar, the two enzymes did not always overlap. The histochemical reaction also revealed two different types of stained cells: a slightly stained subpopulation and a subgroup of deeply stained neurons resembling a Golgi impregnation. These neurons were sparsely spined non-pyramidal cells. Their dendritic arbors were very well stained but their axons were not always evident. In the gray matter, heavily stained neurons showed different dendritic arbor morphologies. However, most of the strongly reactive cells lay in the subjacent white matter, where they presented a more homogenous morphology. Our results demonstrate that the pattern of NADPH-diaphorase activity is similar to that previously described in Old World monkeys.

Histochemical characterization of NADPH-diaphorase activity in area 17 of diurnal and nocturnal primates and rodents

NADPH-diaphorase (NADPH-d) activity was studied comparatively in area 17 of four mammalian species, two primates and two rodents. Three brain hemispheres each from adult capuchin-monkeys, owl-monkeys, agoutis and guinea pigs were fixed with aldehyde fixatives by perfusion and 200 mum sections were submitted to NADPH-d histochemistry, using the indirect malic enzyme method. In all species studied the neuropil pattern of enzyme activity presented a clear layered appearance. In primates, histochemical staining was most intense in layer IVc, while in rodents the highest intensity of the neuropil reaction was in supragranular layers (II and III). Comparison of cell density in grey and white matter showed that the majority of NADPH-d-positive neurones were located in the white matter of primates but not of rodents. Since NADPH-d is a nitric oxide synthase the results are very important for comparative functional studies of neuromediators and their correlations with laminar and modular organization of area 17 of the mammalian brain.