Abstract
Thus far, none of the neuroprotective drugs that have been tested to reduce or prevent secondary ischemic brain damage have been shown clear benefit. We will attempt to identify factors that may be responsible for some of these failures. We also will give our thoughts on how to prevent these pitfalls in the usefulness and criteria for use of animal models for traumatic brain injury to depict human head injury are discussed. Clearly, mechanism-driven trials, in which individual pathophysiological mechanisms are targeted, are more likely to show benefit in this heterogeneous patient population. Other factors, such as the effect of brain penetration, safety and tolerability of the compound, and the interface between the pharmaceutical industry and academics are a major influence in the success of these trials. Furthermore, the way trials have been analyzes in the past may not always have been be the most appropriate to show benefits. It is clear that a multi-targeted approach is necessary to address the complicated and closely related mechanisms seen after traumatic and or ischemic brain damage.
