Characterization of a rat model to study acute neuroinflammation on histopathological, biochemical and functional outcomes.
Neuroinflammation is one of the events occurring after acute brain injuries. The aim of the present report was to characterize a rat model to study acute neuroinflammation on the histopathological, biochemical and functional outcomes. Lipopolysaccharide (LPS), known as a strong immunostimulant, was directly injected into the hippocampus. The spatiotemporal evolution of inducible NOS (iNOS) and cell death was studied from 6 h to 7 days. A perfect time course correlation was observed between iNOS immunoreactivity and iNOS activity showing an acute, expansive and transient iNOS induction in the hippocampus with a peak at 24 h. It was associated with a marked increase in NO metabolite (NO(x)) levels, and a high level of myeloperoxidase (MPO) activity. This inflammation precedes a massive cellular loss including at least neurons and astrocytes, and a drop of constitutive NOS activity, restrictive to the ipsilateral hippocampus from 48 h after LPS injection. Moreover, sensorimotor function impairment occurred from 24 h to 7 days with a maximum at 24 h post-LPS injection. Therefore, we characterized an in vivo model of acute neuroinflammation and neurodegeneration, in relation with a neurological deficit, which may be a powerful tool for mechanistic studies and for further evaluation of the potential neuroprotective agents.
Ambrosini
Andrea
A
Laboratoire de Pharmacologie (UPRES EA 2510), Université René Descartes, 4, avenue de l'Observatoire, 75270 Paris cedex 06, France.
Louin
Gaëlle
G
Croci
Nicole
N
Plotkine
Michel
M
Jafarian-Tehrani
Mehrnaz
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009069:Movement Disorders / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012678:Sensation Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D020521:Stroke / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat