Gliovascular changes precede white matter damage and long‐term disorders in juvenile mild closed head injury
Traumatic brain injury (TBI) is a leading cause of hospital visits in pediatric patients and often leads to long‐term disorders even in cases of mild severity. White matter (WM) alterations are commonly observed in patients months or years after the injury assessed by magnetic resonance imaging (MRI...
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Veröffentlicht in: | Glia 2018-08, Vol.66 (8), p.1663-1677 |
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Sprache: | eng |
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Zusammenfassung: | Traumatic brain injury (TBI) is a leading cause of hospital visits in pediatric patients and often leads to long‐term disorders even in cases of mild severity. White matter (WM) alterations are commonly observed in patients months or years after the injury assessed by magnetic resonance imaging (MRI), but little is known about WM pathophysiology early after mild pediatric TBI. To evaluate the status of the gliovascular unit in this context, mild TBI was induced in postnatal‐day 17 mice using a closed head injury model with two grades of severity (G1, G2). G2 resulted in significant WM edema (increased T2‐signal) and BBB damage (IgG‐extravasation immunostaining) whereas decreased T2 and the increased levels of astrocytic water‐channel AQP4 were observed in G1 mice 1 day post‐injury. Both severities induced astrogliosis (GFAP immunolabeling). No changes in myelin and neurofilament were detected at this acute time point. One month after injury G2 mice exhibited diffusion tensor imaging MRI alterations (decreased fractional anisotropy) accompanied by decreased neurofilament staining in the WM. Both severities induced behavioral impairments at this time point. In conclusion, long‐term deficits and WM changes similar to those found after clinical TBI are preceded by distinct early gliovascular phenotype alterations after juvenile mild TBI, revealing AQP4 as a potential candidate for severity‐based treatments.
Main Points
Early gliovascular alterations precede white matter damage and behavioral deficits after mild juvenile TBI.
Astrocytic AQP4 levels are the highest in the milder severity 24h post‐injury, coinciding with decreased T2 MRI signal. |
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ISSN: | 0894-1491 1098-1136 |
DOI: | 10.1002/glia.23336 |