Mission Connect Mild TBI Translational Research Consortium
Abstract
Brain injury, particularly mild "blast" injuries due to improvised exploding devices, have long term cognitive and behavioral deficits. Key inflammatory cytokine levels (IL-1 and TNFalpha) usually increase after traumatic insults to the brain and contribute to the development of long-term deficits via activation of infiltrated monocytes and resident microglia and astrocytes and impaired vascular function; both resulting in persistent inflammation. Our central hypothesis is that blocking inflammatory cytokine signaling after mild traumatic brain injury (mTBI) will improve outcomes by ameliorating inflammation. Our goal is to develop, implement and assess interventions with two FDA approved drugs in two rat models of mTBI that will ameliorate the mTBI-induced cognitive and behavioral deficits. We have validated the use of a number of biomarkers that characterize mTBI injury as early as 6h and demonstrated significant behavioral impairment, such as working memory, in our lateral fluid percussion model of mTBI. We have also performed a pilot intervention via ip injection of Kineret, an IL-1 receptor antagonist, at 30 minutes and 6 hours post-mTBI. Preliminary assessments show improvement in working memory and amelioration of the glial inflammation biomarker GFAP. Improved administration and dosages are underway. While our first year focused on outcomes at 6h, this second year focuses on outcomes at 18 days.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA542003
Entities
People
- Claire E. Hulsebosch
- Douglas S. Dewitt
- J. R. Perez-polo
- Pramod K. Dash
- Raymond J. Grill
Organizations
- University of Texas Medical Branch