Progressive Neurodegeneration After Experimental Brain Trauma

2013/12/12 by David J. Loane, Alok Kumar, Bogdan A. Stoica +2 · 501 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · Psychology · #Chronic traumatic encephalopathy #Concussion #Inflammation #Internal medicine #Lesion #Medicine #Microglia #Neurodegeneration #Neuroinflammation #Neuroinflammation and Neurodegeneration Mechanisms #Neuroscience #Pathology #Poison control #Psychiatry #Psychology #S100 Proteins and Annexins #Traumatic Brain Injury and Neurovascular Disturbances #Traumatic brain injury

paper · pdf · doi:10.1097/nen.0000000000000021

published in Journal of Neuropathology & Experimental Neurology 73(1), 14-29 (Oxford University Press)

openalex publication_date 2013/12/12 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/06

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 of neuroinflammation and oxidative stress were significantly elevated at this time point. These data support emerging clinical TBI findings and provide a mechanistic link between TBI-induced chronic microglial activation and progressive neurodegeneration.

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