Related Experiment Video
Updated: Feb 22, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice
Toufik Taib1, Claire Leconte1, Juliette Van Steenwinckel2
1EA4475 - Pharmacologie de la Circulation Cérébrale, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
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.
Insights
Mild traumatic brain injury (TBI) causes neuroinflammation and white matter injury (WMI), leading to sensorimotor and cognitive deficits. This study tracks these changes over three months, revealing key inflammatory and demyelination events.
Area of Science:
- Neuroscience
- Immunology
- Neuropathology
Background:
- Traumatic brain injury (TBI) often results in white matter injury (WMI), contributing to neurological deficits.
- Neuroinflammation, driven by microglial activation, is implicated in WMI following TBI, but its temporal dynamics are poorly understood.
- Understanding the time course of neuroinflammation, WMI, and behavioral changes after mild TBI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temporal progression of neuroinflammation, white matter injury, and associated behavioral disorders after experimental mild TBI in mice.
- To characterize microglial activation phenotypes and their correlation with inflammatory markers (IL-1b) post-mild TBI.
- To assess demyelination and myelin repair markers in the corpus callosum and evaluate sensorimotor and cognitive functions over a 3-month period.
Main Methods:
- Mild TBI was induced in mice using controlled cortical impact.
- Neuroinflammation was assessed by measuring IL-1b protein levels and analyzing gene expression of microglial activation markers.
- White matter injury was evaluated by quantifying myelin proteins (2',3'-cyclic-nucleotide 3'-phosphodiesterase, myelin basic protein, myelin oligodendrocyte glycoprotein) and using transmission electron microscopy.
Main Results:
- Elevated IL-1b protein and a mixed population of microglial phenotypes were observed from 6 hours to 3 days post-TBI, resolving by 7 days.
- Demyelination, indicated by reduced myelin basic protein, occurred bilaterally in the corpus callosum from 7 days to 3 months post-TBI.
- Sensorimotor deficits were evident at 3 days, and cognitive flexibility impairments were observed 3 months after mild TBI.
Conclusions:
- Mild TBI triggers a transient neuroinflammatory response that is followed by sustained white matter injury and long-term behavioral deficits.
- The observed demyelination and cognitive impairments suggest a potential link between early neuroinflammation and chronic WMI.
- This study provides a comprehensive timeline of post-TBI events, offering a valuable model for testing therapeutic strategies targeting WMI and behavioral recovery.
