Gliovascular changes precede white matter damage and long-term disorders in juvenile mild closed head injury

Glia. 2018 Aug;66(8):1663-1677. doi: 10.1002/glia.23336. Epub 2018 Apr 17.


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.

Keywords: AQP4; MRI; astrocyte; mild traumatic brain injury; pediatric; white matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology
  • Brain / pathology
  • Brain Injuries, Traumatic / pathology*
  • Cognition Disorders
  • Head Injuries, Closed / pathology*
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice, Inbred C57BL
  • Time*
  • White Matter / pathology*