Evaluation of pharmacological treatment strategies in traumatic brain injury.
Traumatic brain injury (TBI) is a devastating disease, predominately affecting young people. Although the prognosis for TBI victims has improved in recent years, many survivors of TBI suffer from emotional, cognitive and motor disturbances and a decreased quality of life. In recent years, there has been a rapid increase in the number of pharmacological targets evaluated in clinically-relevant experimental TBI models, showing improved cognitive and motor outcome and decreased loss of brain tissue. Despite the completion of several recent clinical trials using compounds showing neuroprotection in preclinical studies, pharmaceutical treatment strategies with proven clinical benefit are still lacking. This paper reviews the preclinical pharmacological treatment studies evaluated to date in experimental models of TBI. Although human TBI is a complex and multifaceted disease, these studies provide encouraging translational data suggesting that pharmacological compounds, delivered in a clinically-relevant time window, may improve the outcome of TBI patients.
Marklund
Niklas
N
Traumatic Brain Injury Laboratory, Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA. niklas.marklund@akademiska.se
Bakshi
Asha
A
Castelbuono
Deborah J
DJ
Conte
Valeria
V
McIntosh
Tracy K
TK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002154:Calpain / Q000037:antagonists & inhibitors; D061945:Caspase Inhibitors; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D006801:Humans; D009414:Nerve Growth Factors / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission
D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D061945:Caspase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009414:Nerve Growth Factors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D019001:Nitric Oxide Synthase; D002154:Calpain