Ambrosini Andrea, Louin Gaëlle, Croci Nicole, Plotkine Michel, Jafarian-Tehrani Mehrnaz
Laboratoire de Pharmacologie (UPRES EA 2510), Université René Descartes, 4, avenue de l'Observatoire, 75270 Paris cedex 06, France.
J Neurosci Methods. 2005 Jun 15;144(2):183-91. doi: 10.1016/j.jneumeth.2004.11.002. Epub 2004 Dec 19.
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.
神经炎症是急性脑损伤后发生的事件之一。本报告的目的是描述一种大鼠模型,以研究急性神经炎症对组织病理学、生物化学和功能结局的影响。脂多糖(LPS),一种已知的强免疫刺激剂,被直接注射到海马体中。研究了诱导型一氧化氮合酶(iNOS)和细胞死亡从6小时到7天的时空演变。观察到iNOS免疫反应性和iNOS活性之间存在完美的时间进程相关性,表明海马体中iNOS呈急性、扩展性和短暂性诱导,在24小时达到峰值。这与NO代谢物(NO(x))水平的显著增加以及高水平的髓过氧化物酶(MPO)活性相关。这种炎症先于包括至少神经元和星形胶质细胞在内的大量细胞丢失,以及组成型NOS活性的下降,从LPS注射后48小时起局限于同侧海马体。此外,感觉运动功能障碍从24小时持续到7天,在LPS注射后24小时达到最大值。因此,我们描述了一种与神经功能缺损相关的急性神经炎症和神经退行性变的体内模型,这可能是用于机制研究和进一步评估潜在神经保护剂的有力工具。