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

Abstract

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.

COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats

“…iNOS mRNA and protein increased on the ipsilateral side at 24 h with no expression on the contralateral side, correlating to our earlier findings of mild to moderate TBI [10,8]. iNOS is upregulated by transcription factors NFkB, STAT-1, IRF-1 and AP-1 and is a main producer of NO following TBI, causing oxidative stress [24,28].…”

“…Due to the negative nature of the contralateral side, for illustrative purposes this is shown only in males putative differences in inflammatory activity between genders, which may have been undetected in other models of TBI. Comparisons were made between the injured and intact hemispheres, in line with our studies of identical or comparable inflammatory markers [10,31]. Sham-treated animals were excluded as they would be irrelevant to the specific hypothesis and weaken the statistical power in the comparison of groups.…”

“…Sixteen to 80 pictures per animal were analyzed depending on resolution. Quantification of stained cells was done manually by cell counting according to our earlier experience, in 20×-40× magnification [10]. Four to 32 pictures per animal were analyzed.…”

Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats

“…Quantification of Fluoro-Jade, manganese superoxide dismutase (MnSOD), Ox-42 (CD11b), 3-nitrotyrosine (3-NT) and iNOS was done by group blinded manual cell counting in eight sections per animal and marker in the ROI at 20-40Â magnification, according to our earlier study, [29] using a Nikon Eclipse E600 (Nikon, Chiyoda, Tokyo, Japan). Filters used were for Cy3 G-1B (excitation/emission [ex/em] 541-551/590 nm), Alexa 488 and Fluoro-Jade filter fluorescein isothiocyanate (FITC; ex/em 465-495/515-555 nm), DAPI filter (ex/em 340-380/435-485).…”

Role of Nitric Oxide Synthase in the Function of the Central Nervous System under Normal and Infectious Conditions

“…These three isoforms of the enzyme nitric oxide synthase (NOS) that are present in the central nervous system (CNS) can produce nitric oxide (NO). eNOS is expressed in the vascular endothelium and choroid plexus; neuronal NOS is mainly expressed in neuronal cell bodies, especially in the cortex, hippocampus, hypothalamus, olfactory bulb, claustrum, amygdala, and thalamus; and inducible NOS is expressed in macrophages, glial cells, infiltrating neutrophils, and, to some extent, neurons [1]. It has also been reported that eNOS can be found in a subset of neurons and astrocytes and that nNOS can be found at low levels in astrocytes [2].…”