• Ye Xiong, Asim Mahmood, and Michael Chopp.
• Henry Ford Health System, Department of Neurosurgery, Detroit, MI 48202, USA.
• Expert Opin Emerg Drugs. 2009 Mar 1;14(1):67-84.

BackgroundThis review summarizes promising approaches for the treatment of traumatic brain injury (TBI) that are in either preclinical or clinical trials.ObjectiveThe pathophysiology underlying neurological deficits after TBI is described. An overview of select therapies for TBI with neuroprotective and neurorestorative effects is presented.MethodsA literature review of preclinical TBI studies and clinical TBI trials related to neuroprotective and neurorestorative therapeutic approaches is provided.Results/ConclusionNearly all Phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials that seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.

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