iNOS-mediated secondary inflammatory response differs between rat strains following experimental brain contusion

Mattias Günther, Faiez Al Nimer, Caroline Gahm, Fredrik Piehl, Tiit Mathiesen

Abstract

BACKGROUND: Nitric oxide is a key mediator of post-traumatic inflammation in the brain. We examined the expressions of iNOS, nNOS, and eNOS in inbred DA and PVGa rat strains where DA is susceptible to autoimmune neuroinflammation and PVGa-resistant.

METHODS: Parietal contusions using a weight drop model were produced in five rats per genotype. After 24 h, the brains were removed and analyzed using a range of immunohistochemical methods.

RESULTS: PVGa presented significantly increased iNOS expression in infiltrating inflammatory cells in the perilesional area compared to DA (p < 0.05). The amount of w3/13-positive infiltrating inflammatory cells did not differ between strains. eNOS and nNOS expression did not differ between strains. iNOS-positive cells coexpressed neuronal (NeuN), macrophage (ED-1), and leucocyte (w3/13) markers. MnSOD was significantly increased in PVGa (p < 0.05). 3-Nitrotyrosine, a measure of peroxynitrite levels, and fluoro-jade stained neuronal degeneration, did not differ between strains.

CONCLUSIONS: Two inbred rat strains with genetically determined differences in susceptibility to develop autoimmune disease displayed different levels of the inflammatory and anti-inflammatory mediators iNOS and MnSOD, indicating genetic regulation. Interestingly, the increased levels of iNOS did not lead to elevated expression of the neuronal cell-death marker fluoro-jade. The increased iNOS expression was correlated with increased expression of superoxide scavenger MnSOD. Excessive peroxynitrite formation was probably prevented by limitation of available superoxide. Subsequently, the higher expression of potentially deleterious iNOS in PVGa did not result in increased neuronal death.

OriginalsprogEngelsk
TidsskriftActa Neurochirurgica
Vol/bind154
Udgave nummer4
Sider (fra-til)689-97
Antal sider9
ISSN0001-6268
DOI
StatusUdgivet - apr. 2012
Udgivet eksterntJa

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