关键词：炎症；创伤性脑损伤；血脑屏障
摘 要：Mild traumatic brain injury (mTBI), such as mild blast injuries due to improvised exploding devices, result in long term impairment of cognition and behavior. Our hypothesis is that there are inflammatory outcomes to mTBI over time that cause pathogenesis and clinical outcomes. We used an adaptation of rat moderate brain lateral fluid percussion (LFP) brain injury and compared 2 blast models developed by us. We characterized a rat mild blast brain injury model (mBBI) that increased IL- 1 beta and TNF alpha levels, macrophage/microglial and astrocytic activation, and blood brain barrier disruption. We assessed beneficial outcomes after blockade of the IL- 1alpha/beta and TNF alpha receptors in the mLFP brain injury model. We found that blocking the IL-1 /beta and TNFR receptors, singly or in combination, with wo FDA-approved drugs Kineret or Interleukin-1 Receptor Antagonist, IL-1R alpha and Etanercept or antibody to the Tumor Necrosis Factor Receptor improved outcomes by ameliorating inflammation. We also determined an optimal time course of treatment. We also characterized our selected mBBI model of mTBI, the Vanderberg model. We found similar resulting righting reflex response times (RRRT) for the mBBI as compared to the mLFP injury. We determined that there were significant increases in IL-1 beta and TNF alpha levels, macrophage/microglial and astrocytic activation, and phosphorylated Tau (p-Tau) levels, the latter indicative of neuroencephalopathy, in the injured cortex, hippocampus, thalamus and amygdala. Whereas there was an apparent correlation between the RRRT values and the p-Tau levels, general inflammatory responses were more threshold-triggered. These results suggest potential therapies for mild blast injuries.