Journal of neurotrauma
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Journal of neurotrauma · Mar 2014
The Cysteine Protease Cathepsin B is a Key Drug Target and Cysteine Protease Inhibitors are Potential Therapeutics for Traumatic Brain Injury.
There are currently no effective therapeutic agents for traumatic brain injury (TBI), but drug treatments for TBI can be developed by validation of new drug targets and demonstration that compounds directed to such targets are efficacious in TBI animal models using a clinically relevant route of drug administration. The cysteine protease, cathepsin B, has been implicated in mediating TBI, but it has not been validated by gene knockout (KO) studies. Therefore, this investigation evaluated mice with deletion of the cathepsin B gene receiving controlled cortical impact TBI trauma. ⋯ E64d treatment was effective even when administered 8 h after injury, indicating a clinically plausible time period for acute therapeutic intervention. These data demonstrate that a cysteine protease inhibitor can be orally efficacious in a TBI animal model when administered at a clinically relevant time point post-trauma, and that E64d-mediated improvement of TBI is primarily the result of inhibition of cathepsin B activity. These results validate cathepsin B as a new TBI therapeutic target.
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Journal of neurotrauma · Mar 2014
Infection Rates and Associated Factors In Pediatric Severe Traumatic Brain Injury.
Abstract Infections can increase medical costs and worsen patient outcomes. Our aims in pediatric severe traumatic brain injury (sTBI) patients were to determine the infection and fever rates, and to report on associated clinical, imaging, treatment, and outcome factors. We included 180 sTBI patients (presedation Glasgow Coma Scale ≤ 8 and Maximum Abbreviated Injury Scale ≥ 4) admitted to our pediatric intensive care unit. ⋯ In summary, infections were prevalent in sTBI patients and were associated with greater head-imaging abnormalities and use of ICP-lowering therapies. Hypertonic saline administration was strongly associated with infection, but further analyses are required to determine the nature of this relationship. Fever was a poor indicator of infection after sTBI.