Related Experiment Video
Updated: Feb 11, 2026
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Published on: February 7, 2025
Gliovascular changes precede white matter damage and long-term disorders in juvenile mild closed head injury
Beatriz Rodriguez-Grande1, Andre Obenaus1,2,3,4,5, Aleksandra Ichkova1
1CNRS UMR5287, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, University of Bordeaux, Bordeaux, France.
Insights
Mild traumatic brain injury (TBI) in juvenile mice causes early white matter changes, including altered AQP4 levels and astrogliosis. These changes precede long-term deficits and suggest potential therapeutic targets for pediatric TBI.
Area of Science:
- Neuroscience
- Pediatric Traumatology
- Neuroimaging
Background:
- Traumatic brain injury (TBI) is a significant cause of pediatric hospitalizations, often leading to long-term neurological disorders.
- White matter (WM) alterations are common sequelae of TBI, but early pathophysiology after mild pediatric TBI remains poorly understood.
- The role of the gliovascular unit in acute mild TBI is an area requiring further investigation.
Purpose of the Study:
- To investigate early white matter (WM) pathophysiology and gliovascular unit changes following mild traumatic brain injury (TBI) in juvenile mice.
- To compare the effects of two grades of TBI severity on WM integrity and cellular responses.
- To identify potential biomarkers and therapeutic targets for acute pediatric TBI.
Main Methods:
- Mild TBI was induced in juvenile mice (postnatal day 17) using a closed head injury model with two severity grades (G1, G2).
- Assessments included MRI (T2-signal, diffusion tensor imaging), blood-brain barrier (BBB) integrity assays (IgG extravasation), and immunohistochemistry for glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), myelin, and neurofilaments.
- Behavioral tests were conducted one month post-injury.
Main Results:
- Grade 2 (G2) TBI caused significant WM edema and BBB damage, while Grade 1 (G1) TBI showed decreased T2 signal and increased AQP4 levels.
- Both TBI severities induced astrogliosis (GFAP) acutely, with no immediate changes in myelin or neurofilaments.
- One month post-injury, G2 mice exhibited altered fractional anisotropy (MRI) and reduced neurofilament staining, alongside behavioral impairments in both groups.
Conclusions:
- Distinct early gliovascular alterations, including changes in AQP4 and astrogliosis, occur after juvenile mild TBI.
- These acute changes precede the development of long-term WM deficits and behavioral impairments observed in mouse models.
- AQP4 emerges as a potential therapeutic target for modulating disease severity in pediatric TBI.
Abstract:
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.
Related Concept Videos
02:49Classifying Matter by State
03:35Classifying Matter by Composition
According to its composition, the matter can be classified into two broad categories — pure substances and mixtures.
A pure substance is a form of matter that has a constant composition throughout with uniform properties. For example, any sample of sucrose has the same composition and same physical properties, such as melting point, color, and sweetness, regardless of the source from which it is isolated.
A mixture is composed of two or...
02:57Physical and Chemical Properties of Matter
02:59The Atomic Theory of Matter
01:13What is Matter?
01:20States of Matter
Scientists have discovered a fourth state of matter, plasma, that occurs naturally in the interiors...