title: Characterization of a rat model to study acute neuroinflammation on histopathological, biochemical and functional outcomes.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacologie (UPRES EA 2510), Université René Descartes, 4, avenue de l'Observatoire, 75270 Paris cedex 06, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ambrosini
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Louin
authors.forename: Nicole
authors.initials: N
authors.lastname: Croci
authors.forename: Michel
authors.initials: M
authors.lastname: Plotkine
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Jafarian-Tehrani
mesh_terms: 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
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat