Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 31; no. 12; pp. 596 - 604
• Main Authors: Loane, David J, Faden, Alan I
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2010
• Subjects: Advanced Basic Science; Animals; Brain - drug effects; Brain Injuries - complications; Brain Injuries - drug therapy; Clinical Trials as Topic - methods; Clinical Trials as Topic - standards; Drug Delivery Systems - methods; Drug Evaluation, Preclinical - standards; Drugs, Investigational - therapeutic use; Humans; Nerve Degeneration - complications; Nerve Degeneration - drug therapy; Nerve Degeneration - prevention & control; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Translational Medical Research - methods
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2010.09.005

Traumatic brain injury (TBI) causes secondary biochemical changes that contribute to subsequent tissue damage and associated neuronal cell death. Neuroprotective treatments that limit secondary tissue loss and/or improve behavioral outcome have been well established in multiple animal models of TBI. However, translation of such neuroprotective strategies to human injury have been disappointing, with the failure of more than thirty controlled clinical trials. Both conceptual issues and methodological differences between preclinical and clinical injury have undoubtedly contributed to these translational difficulties. More recently, changes in experimental approach, as well as altered clinical trial methodologies, have raised cautious optimism regarding the outcomes of future clinical trials. Here we critically review developing experimental neuroprotective strategies that show promise, and we propose criteria for improving the probability of successful clinical translation.