Abstract
Traumatic brain injury (TBI) results in white matter injury (WMI) that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i) neuroinflammation, (ii) WMI and (iii) behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i) For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii) Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii) TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model of mild TBI. This model could help to validate a pharmacological strategy to prevent post-traumatic WMI and behavioral disorders following mild TBI.
Highlights
Traumatic brain injury (TBI) is a leading cause of mortality and disability that mainly affects young adults in industrialized countries and that imposes a substantial social and economic burden on the community [1,2]
There is no data on mild TBI, we investigated the time courses of neuroinflammation, mainly microglial phenotypes, white matter injury (WMI), and behavior at selected time points ranging from 6 hours to 3 months after a mild TBI induced by cortical impact (CCI) in mice
IL1b mRNA associated with pro-inflammatory phenotype and IL1rn mRNA associated with immunoregulatory phenotype were increased at 6 hours after mild TBI (Fig 4)
Summary
Traumatic brain injury (TBI) is a leading cause of mortality and disability that mainly affects young adults in industrialized countries and that imposes a substantial social and economic burden on the community [1,2]. As primary injury occurs immediately after trauma, prevention is the only possibility to limit this type of injury. The latter leads to secondary injury such as white matter injury (WMI) and neuroinflammation [3]. These events may develop from hours to days, weeks, months or even years following the impact, providing a window of opportunity for therapeutic intervention. Myelin pathology can result from either loss of myelin due to loss of axons, and/or from secondary damage that cause oligodendrocyte loss with subsequent demyelination of viable/intact axons [12]. Demyelination was recently evidenced in mice 12 months after mild TBI [17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
