Age-associated inflammatory response changes after repeated closed-head traumatic brain injury
Indiana University Purdue University Indianapolis
Andrew Brumett1, Tyler Nguyen2,3,4, Natalie Nguyen3,4, Fletcher A. White2,3,4
1 Indiana University, Purdue University of Indianapolis, 2 Stark Neuroscience Research Institute, 3 Department of Anesthesia, Indiana University School of Medicine, 4 Richard L. Roudebush VA Medical Center, Indianapolis, Indiana.
Mild traumatic brain injury (mTBI) is a common neurological injury and is associated with central and peripheral inflammation. A principal mechanism of this inflammation is the NLRP3 inflammasome cascade. This activated caspase-1 dependent neuroinflammation is often associated with chronic nociplastic pain states. Aging may be a major contributor to the worsening of clinical outcomes.
To model the effect of aging, a luciferase-based caspase-1 reporter mouse line was used to assess inflammation post-repeated mTBI in vivo. Two groups young (4-6 month) (n=4) and aged (18-20 months) (n=4) animals underwent a skull-thinning procedure and repetitive closed-head control impact (CCI). In vivo bioluminescence imaging was utilized to monitor caspase-1 mediated inflammation. Three injuries, each separated by 1 week, were performed and each followed by IVIS imaging, von Frey, and Grimace behavioral assays. Three timepoints were also observed after the third injury to assess the chronic nature of the inflammation.
The aged animals showed a significant increase in caspase-1 activation at the 3 days after 3rd injury timepoint in both the brain and paw regions compared to young animals. There were no significant differences in either behavioral assay between the young and aged animals and any timepoint.
This study will be repeated with increased group sizes to increase predictive effect and decrease standard errors.
Translational/Human Health Impact:
Understanding the role of inflammasome-caspase 1 in TBI pathophysiology will enable more effective therapeutic strategies in treating post-traumatic pain.