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Updated: May 26, 2025
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Published on: February 7, 2025
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Christophe J Dubois1, J Yan2, A Obenaus2
1Centre d'Études Biologiques de Chizé-Centre National de la Recherche Scientifique (CEBC-CNRS), UMR 7372 CNRS/Université de La Rochelle; Univ. Bordeaux, CNRS, CRMSB, UMR 5536; cdubois@rmsb.u-bordeaux.fr.
Insights
A new juvenile concussion model, CHILD, mimics long-term brain injury symptoms in mice. This model is crucial for understanding childhood concussions and developing future therapies for persistent neurological issues.
Area of Science:
- Neuroscience
- Traumatic Brain Injury Research
- Pediatric Health
Background:
- Childhood concussions and mild traumatic brain injuries (mTBI) lead to significant long-term health problems.
- The underlying cellular and molecular mechanisms of these injuries remain poorly understood.
- Existing animal models do not fully replicate the complex features of human concussions.
Purpose of the Study:
- To develop a novel juvenile concussion model that recapitulates both early and long-term clinical symptoms.
- To create a tool for investigating the pathophysiology of pediatric TBI and testing therapeutic strategies.
Main Methods:
- A Closed Head Injury with Long-term Disorder (CHILD) model was developed using post-natal day 17 mice.
- Concussive force was delivered via an electromagnetic impactor to unrestrained, lightly anesthetized mice, allowing head rotation.
- Injury severity was modulated by impactor settings, and outcomes were assessed through behavioral tests, neuroimaging, and histological analysis.
Main Results:
- The CHILD model, without skull fracture or conventional neuroimaging changes, induced progressive neuronal death and altered diffusion MRI.
- Key findings include modified neuronal activity and plasticity, increased gliosis, and age-progressive behavioral deficits.
- The model's injury severity can be adjusted to mimic the heterogeneity of human juvenile concussions.
Conclusions:
- The CHILD model effectively replicates early and long-term features of clinical concussion in juvenile patients.
- This model provides a valuable platform for advancing research into the chronic sequelae of pediatric TBI.
- Further investigation using the CHILD model can facilitate the development of targeted therapies for concussion recovery.
Abstract:
Concussions and mild traumatic brain injuries (mTBI) during childhood represent a significant health endangerment, with many patients later in life exhibiting debilitating physiological, neurological, and psychosocial outcomes. The cellular and molecular pathophysiological mechanisms are relatively unknown, and this significant gap effectively precludes investigations into specific therapeutic strategies to mitigate chronic sequelae. No single animal concussion model recapitulates all the features reported in human subjects, and current models are designed to answer specific research questions. We set out to develop a juvenile concussion that recapitulates clinical early, and long-term symptomology encountered, termed Closed Head Injury with Long-term Disorder (CHILD). In this model, a concussive force via an electromagnetic impactor is delivered to the head of a lightly anesthetized unrestrained post-natal day 17 (P17) mouse, allowing free rotation of the head. Mice are placed on a tightly stretched tin foil across a stereotactic device, and the impactor is carefully aligned with the targeted cortical region. The electromagnetic impactor facilitates the selection of impact depth, dwell, and duration to determine injury severity. A strength of this model is that it allows head rotation, an important clinical feature. After impact, mice are immediately monitored for righting time and time to explore their environment, followed by their return to their dam. Increasing the severity of concussion results in intracranial bleeds in a subset of mice. Mice can be routinely monitored for behavior and neuroimaging over their lifespan, as desired. Various injury severities mimic the heterogeneous nature of juvenile concussions. The current standard CHILD model exhibits no skull fracture, no observable conventional neuroimaging change (similar to clinical), but leads to progressive and persistent neuronal death, altered diffusion MRI, modified neuronal activity and plasticity, increased gliosis, and progressive behavioral perturbations with age. In summary, this CHILD model mimics the early and long-term features observed in many clinical concussion patients.
