Pharmacology of Traumatic Brain Injury: Where Is the “Golden Bullet”?

Abstract

Traumatic brain injury (TBI) represents a major health care problem and a significant socioeconomic challenge worldwide. In the United States alone, approximately 1.5 million patients are affected each year, and the mortality of severe TBI remains as high as 35%-40%. These statistics underline the urgent need for efficient treatment modalities to improve posttraumatic morbidity and mortality. Despite advances in basic and clinical research as well as improved neurological intensive care in recent years, no specific pharmacological therapy for TBI is available that would improve the outcome of these patients. Understanding of the cellular and molecular mechanisms underlying the pathophysiological events after TBI has resulted in the identification of new potential therapeutic targets. Nevertheless, the extrapolation from basic research data to clinical application in TBI patients has invariably failed, and results from prospective clinical trials are disappointing. We review the published prospective clinical trials on pharmacological treatment modalities for TBI patients and outline future promising therapeutic avenues in the field.

Role of synucleins in traumatic brain injury — An experimental in vitro and in vivo study in mice

“…TBI results in an array of pathophysiological responses and clinical consequences similar to a subset of those observed in PD and other NDDs including accumulation of aggregated synucleins and disturbances in the synuclein metabolism (Smith et al, 2003;Uryu et al, 2007;Beauchamp et al, 2008;Blennow et al, 2012). α-Synuclein is by far the best known and most studied among the three members of the synuclein family, due to its strong link with PD, the second most common human NDDs.…”

“…At corresponding time-points, mice were euthanized, and brain tissue was surgically removed, snap-frozen in liquid nitrogen and stored at − 80°C for future analysis by immunohistochemistry. Assessment of injury severity and modality was carried out as described previously (Leinhase et al, 2006;Beauchamp et al, 2008;Flierl et al, 2009).…”

High Ca2+ Influx During Traumatic Brain Injury Leads to Caspase-1-Dependent Neuroinflammation and Cell Death

“…TBI has been classified as primary and secondary. Primary injury is the result of mechanical forces applied to the skull and brain at the time of impact such as skull fracture, brain contusion, rupturing of blood vessels, and intracranial hemorrhage [2,3]. Secondary injuries are characterized by a complex cascade of molecular, neurochemical, and cellular events initiated by the trauma that can lead to elevated intracranial pressure, blood-brain barrier (BBB) disruption, neuroinflammation, brain edema, cerebral hypoxia, ischemia, and delayed neurodegeneration [4][5][6].…”

Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats

“…Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide [1]. Oxygen free radical-mediated lipid peroxidation, inflammation, and brain edema formation appear to be fundamental mechanisms of secondary damage in TBI [2][3][4].…”