Progressive neurodegeneration after experimental brain trauma: association with chronic microglial activation

Journal of Neuropathology and Experimental Neurology
David J LoaneAlan I Faden

Abstract

Recent clinical studies indicate that traumatic brain injury (TBI) produces chronic and progressive neurodegenerative changes leading to late neurologic dysfunction, but little is known about the mechanisms underlying such changes. Microglial-mediated neuroinflammationis an important secondary injury mechanism after TBI. In human studies, microglial activation has been found to persist for many years after the initial brain trauma, particularly after moderate to severe TBI. In the present study, adult C57Bl/6 mice were subjected to single moderate-level controlled cortical impact and were followed up by longitudinal T2-weighted magnetic resonance imaging in combination with stereologic histologic assessment of lesion volume expansion, neuronal loss, and microglial activation for up to 1 year after TBI. Persistent microglial activation was observed in the injured cortex through 1 year after injury and was associated with progressive lesion expansion, hippocampal neurodegeneration, and loss of myelin. Notably, highly activated microglia that expressed major histocompatibility complex class II (CR3/43), CD68, and NADPH oxidase (NOX2) were detected at the margins of the expanding lesion at 1 year after injury; biochemical markers o...Continue Reading

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Citations

Aug 7, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·David J LoaneAlan I Faden
Nov 26, 2015·Journal of Neurotrauma·Jacob W SkoviraAlan I Faden
Oct 22, 2015·Journal of Neurotrauma·Alok KumarDavid J Loane
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Nov 26, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Alan I Faden, David J Loane
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