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Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation
Authors:Shruti V. Kabadi  Alan I. Faden
Affiliation:Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research (STAR), National Study Center for Trauma and EMS, University of Maryland School of Medicine, Baltimore, MD 21201, USA; E-Mail:
Abstract:Traumatic brain injury (TBI) induces secondary biochemical changes that contribute to delayed neuroinflammation, neuronal cell death, and neurological dysfunction. Attenuating such secondary injury has provided the conceptual basis for neuroprotective treatments. Despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed. In part, these failures likely reflect methodological differences between the clinical and animal studies, as well as inadequate pre-clinical evaluation and/or trial design problems. However, recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation. Here we critically analyze the current limitations and translational opportunities for developing successful neuroprotective therapies for TBI.
Keywords:experimental head injury   clinical trial design   translational challenges   multipotential neuroprotective approaches   programmed cell death   caspase-dependent and AIF-mediated cell death   microglial and astrocyte activation   autophagy
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