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 mechanis ms leading to posttraumatic tissue damage and associated neurological dysfu nction. The concept of delayed or secondary tissue injury has strong experi mental support and a cascade of secondary injury factors has been delineate d.(1,2) These observations have led to the application of targeted pharmaco therapies, whose aim is to block specific pathobiological pathways.(2,3) S uch research has been aided by the development of rodent models of head inj ury that simulate critical components of clinical neurotrauma, as well as b y the development of novel neuroprotective agents.(3,4) These experimental studies have identified mechanisms of delayed tissue damage and have demons trated the effectiveness of a number of pharmacological treatment strategie s.(1-4) However, despite this enormous experimental promise, the clinical s tudies to date have been disappointing.(5,6) Here we explore the conceptual and methodological issues that have contributed to this discrepancy betwee n preclinical and clinical studies.