Challenges in translating the efficacy of neuroprotective agents in experimental models into knowledge of clinical benefits in head injured patients

Many agents have been shown to reduce brain damage in experimental models o f brain injury; this is proving difficult to translate into improved outcom e of patients for reasons that are reviewed in this article. It is possible that, even if fundamental mechanisms are similar, injury processes modelle d experimentally may be proportionately less important in human cases, and there also may have been insufficient attention to ensuring that dosage reg imens far patients are therapeutically appropriate both in terms of concent ration and time window. The distribution of outcomes after head injury mean s that, in unselected populations, a proportional improvement to the extent usually sought may be difficult to achieve. Future studies may need to con sider more extensive work in "targeted populations" (selected by type and s everity of damage) as a preliminary step before proceeding to definitive st udies of efficacy, in which expectations of effect need to be lower and cor respondingly large numbers of patients studied. Recant experience in the ev aluation of glutamate NMDA antagonists is reviewed.