Mission Connect Mild TBI Translational Research Consortium

Abstract

Mild traumatic brain injury (mTBI), particularly mild blast injuries due to improvised exploding devices, result in long term impairment of cognition and behavior. Our hypothesis is that there are inflammatory consequences to mTBI that persist over time and in part cause the resultant pathogenesis and clinical outcomes. We used an adaptation (1 atm pressure) of the moderate to severe brain lateral fluid percussion (LFP) brain injury rat model. Our mild LFP (mLFP) injury resulted in acute increases in IL-1 / and TNF levels, macrophage/ microglial and astrocytic activation, and blood brain barrier (BBB) disruption; which may contribute to brain pathology. These results suggest therapeutic opportunities to treat mTBI via blockade of the IL-1 / and TNF receptors. We further hypothesize that blockade of these receptors, IL-1 and IL-1 , both bind to the IL- 1R receptor, will block inflammatory cytokine signaling after mTBI and improve outcomes by ameliorating inflammation. Our goal is to develop, implement and assess interventions with two FDA-approved drugs (Kineret or Interleukin-1 Receptor Antagonist, IL-1Ra and Etanercept or antibody to the Tumor Necrosis Factor Receptor alpha, TNF ) singly or in combination in a rat model of mTBI (mild lateral fluid percussion or mLFP) that will ameliorate the mTBI-induced inflammation and therefore the resultant neuropathology and neurological deficits. We also proposed to test our hypothesis on a blast model of mTBI on two models. An earlier model relied on an injury consisting of a primary blast exposure followed by blunt impact injury, the Vanderberg model. The other more recently implemented model is the Advanced Blast Simulator. During this last year, we assessed the beneficial effects of individual vs combined treatment with Kineret and Etanercept; we also determined an optimal time course of treatment.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2012
Accession Number
ADA568970

Entities

People

  • Claire E. Hulsebosch
  • Douglas S. Dewitt
  • J. R. Perez-polo
  • Raymond J. Grill

Organizations

  • University of Texas Medical Branch

Tags

DTIC Thesaurus Topics

  • Blood
  • Blood-Brain Barrier
  • Brain
  • Brain Injuries
  • Cell Physiological Processes
  • Cells
  • Cytokines
  • Dermatologic Agents
  • Growth Factors
  • Inflammation
  • Medical Personnel
  • Nervous System
  • Neuroglia
  • Neurons
  • Peptide Growth Factors
  • Peptides
  • Proteins

Fields of Study

  • Medicine

Readers

  • Neurotrauma and Rehabilitation Medicine.
  • Oncology (Cancer Research).
  • Traumatic Brain Injury (TBI) and Cognitive Aging in the Guam and Border Populations Affected by Alzheimer's Disease and Tau-Associated Dementias.