• José Luís Alves, Joana Rato, and Vitor Silva.
• Department of Neurosurgery, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. Electronic address: jlmonteiroalves@gmail.com.
• World Neurosurg. 2019 Oct 1; 130: 115-121.

AbstractTraumatic brain injury (TBI) represents a major health care problem and a significant social and economic issue worldwide. Considering the generalized failure in introducing effective drugs and clinical protocols, there is an urgent need for efficient treatment modalities, able to improve devastating posttraumatic morbidity and mortality. In this work, the status of brain trauma research is analyzed in all its aspects, including basic and translational science and clinical trials. Implicit and explicit challenges to different lines of research are discussed and clinical trial structures and outcomes are scrutinized, along with possible explanations for systematic therapeutic failures and their implications for future development of drug and clinical trials. Despite significant advances in basic and clinical research in recent years, no specific therapeutic protocols for TBI have been shown to be effective. New potential therapeutic targets have been identified, following a better understanding of pathophysiologic mechanisms underlying TBI, although with disappointing results. Several reasons can be pinpointed at different levels, from inaccurate animal models of disease to faulty preclinical and clinical trials, with poor design and subjective outcome measures. Distinct strategies can be delineated to overcome specific shortcomings of research studies. Identifying and contextualizing the failures that have dominated TBI research is mandatory. This review analyzes current approaches and discusses possible strategies for improving outcomes.Copyright © 2019 Elsevier Inc. All rights reserved.

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