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Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury
Published on: August 16, 2019
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A Projectile Concussive Impact Model Produces Neuroinflammation in Both Mild and Moderate-Severe Traumatic Brain
Lindsay T Michalovicz1, Kimberly A Kelly1, Travis J A Craddock2,3,4,5
1Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26508, USA.
Brain Sciences
|May 16, 2023
Summary
This study developed a new model for traumatic brain injury (TBI) in rats using different projectiles to simulate mild and moderate-severe injuries. The findings highlight the role of neuroinflammation in TBI outcomes.
Area of Science:
- Neuroscience
- Neurology
- Trauma Research
Background:
- Traumatic brain injury (TBI) is a significant cause of death and disability, affecting millions annually.
- Even mild TBIs can lead to long-term neurological issues like cognitive impairment and fatigue due to neuroinflammation and neural damage.
- Existing TBI models may not fully capture the spectrum of injury severity and its underlying mechanisms.
Purpose of the Study:
- To modify the projectile concussive impact (PCI) model to create variable-severity closed-head injuries.
- To evaluate neurobehavioral, neuroinflammatory, and neural damage endpoints in rats following mild and moderate-severe TBI.
- To investigate the association between neuroinflammation and TBI severity using computational modeling.
Main Methods:
- Modified a PCI model using aluminum (mild TBI) and stainless-steel (moderate-severe TBI) projectiles in adult male Sprague Dawley rats.
- Assessed neurobehavioral deficits, neuroinflammation markers (cytokine mRNA), neuronal degeneration, and survival rates up to 72 hours post-injury.
- Utilized a computational model to analyze neuron-glia interactions based on cytokine expression.
Main Results:
- Stainless-steel projectile TBI induced moderate-severe outcomes: prolonged unconsciousness, impaired neurobehavior, hematoma, death, significant neuronal degeneration, and widespread neuroinflammation.
- Aluminum projectile TBI resulted in mild TBI characteristics: transient unconsciousness without deficits, no neurodegeneration, and mild neuroinflammation.
- Computational analysis linked moderate-severe TBI to a strong neuroinflammatory state, while mild TBI showed intermediate neuron-glia interactions.
Conclusions:
- The modified PCI model effectively replicates mild and moderate-severe TBI, offering valuable tools for research.
- Neuroinflammation plays a critical role in the pathophysiology of TBI, with severity-dependent effects.
- These models facilitate the study of neuroinflammation and chronic pathophysiology in long-term TBI outcomes.
