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Mission Connect Mild TBI Translational Research Consortium

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Annual rept. 1 Aug 2011-31 Jul 2012

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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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

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