Cause and prevention of demyelination in a model multiple sclerosis lesion

摘要: OBJECTIVE: Demyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination occur in the relative absence lymphocytes, with distinctive characteristics suggestive tissue energy deficit. The objective was to examine an experimental model early sclerosis lesion identify pathogenic mechanisms opportunities for therapy. METHODS: Demyelinating were induced rat spinal dorsal column by microinjection lipopolysaccharide, examined immunohistochemically at different stages development. efficacy treatment inspired oxygen 2 days following induction evaluated. RESULTS: not centered on injection site, rather formed 1 week later white-gray matter border, preferentially including ventral watershed. Lesion formation preceded transient period hypoxia increased production superoxide nitric oxide. Oligodendrocyte numbers decreased site shortly afterward, prior demyelination. Lesions inherent susceptibility hypoxia, as revealed exposure naive animals hypoxic environment. Notably, raising (80%, normobaric) during significantly reduced or prevented INTERPRETATION: characteristic least some arise vascular watershed activation innate immune provoke oxide formation, all which compromise cellular sufficiency. eliminated increasing alleviate hypoxia. Ann Neurol 2016;79:591-604.