Targets of Neuroprotection and Review of Pharmacological Interventions in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major contributor to disability and death worldwide, and manifests in cognitive, behavioral, and motor impairment. Although there have been numerous pre-clinical studies that have identified promising pharmacologic treatments, to date, all Phase III clinical trials have failed. Thus, this is a priority area for ongoing research and development. Treatment strategies have traditionally focused on neuroprotection of the injured brain to reduce secondary injury, neuronal death, and lesion size. The aim of this minireview is to describe the secondary injury pathophysiology of TBI and give an examination of key targets of neuroprotection, select Phase III trials that have been undertaken, and future possibilities for successful drug development. SIGNIFICANCE STATEMENT: This minireview provides an up-to-date summary of the key Phase III clinical trials that have been undertaken in the development of a neuropharmacological treatment for traumatic brain injury. The article discusses the key targets for treatment, the potential reasons for the lack of translation of promising pre-clinical compounds, and the most promising avenues for future development.