Neuroprotection and traumatic brain injury: the search continues.

During the last decade, experimental studies of traumatic brain injury (TBI) have provided important new insights into the pathophysiological mechanisms leading to posttraumatic tissue damage and associated neurological dysfunction. The concept of delayed or secondary tissue injury has strong experimental support and a cascade of secondary injury factors has been delineated. 1,2 These observations have led to the application of targeted pharmacotherapies, whose aim is to block specific pathobiological pathways. 2,3 Such research has been aided by the development of rodent models of head injury that simulate critical components of clinical neurotrauma, as well as by the development of novel neuroprotective agents. 3,4 These experimental studies have identified mechanisms of delayed tissue damage and have demonstrated the effectiveness of a number of pharmacological treatment strategies, 1-4 However, despite this enormous experimental promise, the clinical studies to date have been disappointing, 5,6 Here we explore the conceptual and methodological issues that have contributed to this discrepancy between preclinical and clinical studies.