The simple model versus the super model: Translating experimental traumatic brain injury research to the bedside

Despite considerable investigation in rodent models of traumatic brain inju ry (TBI), no novel therapy has been successfully translated from bench to b edside. Although well-described limitations of clinical trails may account for these failures, several modeling factors may also contribute to the lac k of therapeutic translation from the laboratory to the clinic. Specificall y, models of TBI may omit one or more critical, clinically relevant pathoph ysiologic features. In this invited review article, the impact of the limit ed incorporation of several important clinical pathophysiologic factors in TBI, namely secondary insults (i.e., hypotension and/or hypoxemia), coma, a nd aspects of standard neurointensive care monitoring and management strate gies (i.e., intracranial pressure [ICP] monitoring and ICP-directed therapi es, sedation, mechanical ventilation, and cardiovascular support) are discu ssed. Comparative studies in rodent and large animal models of TBI (which m ay, in some cases, represent super models) are also presented. We conclude that therapeutic breakthroughs will likely require a multidisciplinary appr oach, involving investigation in a range of models, including clinically re levant modifications of established animal models, along with development a nd application of new innovations in clinical trial design.