Document Type
Article
Publication Date
4-6-2023
Publication Title
Brain Sciences
Keywords
inflammation, logic modeling, neural damage, neuroimmune, projectile concussive impact;, traumatic brain injury.
ISSN
2076-3425
Volume
13
Issue/No.
4
First Page
623
Abstract
Traumatic brain injury (TBI) is a major cause of death and disability and is experienced by nearly 3 million people annually as a result of falls, vehicular accidents, or from being struck by or against an object. While TBIs can range in severity, the majority of injuries are considered to be mild. However, TBI of any severity has the potential to have long-lasting neurological effects, including headaches, cognitive/memory impairments, mood dysfunction, and fatigue as a result of neural damage and neuroinflammation. Here, we modified a projectile concussive impact (PCI) model of TBI to deliver a closed-head impact with variable severity dependent on the material of the ball-bearing projectile. Adult male Sprague Dawley rats were evaluated for neurobehavioral, neuroinflammatory, and neural damage endpoints both acutely and longer-term (up to 72 h) post-TBI following impact with either an aluminum or stainless-steel projectile. Animals that received TBI using the stainless-steel projectile exhibited outcomes strongly correlated to moderate-severe TBI, such as prolonged unconsciousness, impaired neurobehavior, increased risk for hematoma and death, as well as significant neuronal degeneration and neuroinflammation throughout the cortex, hippocampus, thalamus, and cerebellum. In contrast, rats that received TBI with the aluminum projectile exhibited characteristics more congruous with mild TBI, such as a trend for longer periods of unconsciousness in the absence of neurobehavioral deficits, a lack of neurodegeneration, and mild neuroinflammation. Moreover, alignment of cytokine mRNA expression from the cortex of these rats with a computational model of neuron-glia interaction found that the moderate-severe TBI produced by the stainless-steel projectile strongly associated with the neuroinflammatory state, while the mild TBI existed in a state between normal and inflammatory neuron-glia interactions. Thus, these modified PCI protocols are capable of producing TBIs that model the clinical and experimental manifestations associated with both moderate-severe and mild TBI producing relevant models for the evaluation of the potential underlying roles of neuroinflammation and other chronic pathophysiology in the long-term outcomes associated with TBI.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
NSUWorks Citation
Michalovicz, Lindsay T; Kelly, Kimberly A; Craddock, Travis J. A.; and O'Callaghan, James P, "A Projectile Concussive Impact Model Produces Neuroinflammation in Both Mild and Moderate-Severe Traumatic Brain Injury." (2023). HPD Articles. 224.
https://nsuworks.nova.edu/hpd_facarticles/224
ORCID ID
0000-0002-6128-8760, 0000-0002-1146-3137, 0000-0001-7244-6317,
DOI
10.3390/brainsci13040623
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland.
Comments
This work was supported by Congressionally Directed Medical Research Program, Gulf War Illness Research Program (CDMRP GWIRP) grant CDMRPL-19-0-GW180106 (L.T. Michalovicz, PI) and a pilot project supported by CDMRP GWIRP W81XWH-13-2-0072 (K. Sullivan, PI), as well as intramural funding from the Centers for Disease Control and Prevention—National Institute for Occupational Safety and Health (K.A. Kelly/J.P. O’Callaghan, PIs).