Year: 2014
Type: article
Abstract: Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.
Source: Shock
Authors: Marcin F. Osuchowski, Daniel G. Remick, James A. Lederer, Charles H. Lang, Ansgar O. Aasen, Mayuki Aibiki, Luciano C. Azevedo, Soheyl Bahrami, Mihaly Boros, Robert Cooney, Salvatore Cuzzocrea, Yong Jiang, Wolfgang G. Junger, Hiroyuki Hirasawa, Richard S. Hotchkiss, Xiang-An Li, Peter Radermacher, Heinz Redl, Reinaldo Salomao, Amin Soebandrio, Christoph Thiemermann, Jean-Louis Vincent, Peter Ward, Yong-Ming Yao, Huang-Ping Yu, Basilia Zingarelli, Irshad H. Chaudry
Institutions: Boston University, Oslo University Hospital, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Chiba University, Queen Mary University of London, University of Szeged, University of Alabama at Birmingham, Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Hospital Sírio-Libanês, William Harvey Research Institute, Southern Medical University, Harvard University, Washington University in St. Louis, Erasmus Hospital, University of Kentucky, SUNY Upstate Medical University, University of Michigan, University of Messina, Pennsylvania State University, Chinese PLA General Hospital, First Affiliated Hospital of Chinese PLA General Hospital, Penn State Milton S. Hershey Medical Center, Chang Gung Memorial Hospital, Hospital São Paulo, Universidade Federal de São Paulo, Cincinnati Children's Hospital Medical Center, University of Indonesia, Ehime University
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: green
Awards: Neutrophil activation and trauma, Cytokine Regulation of Muscle Protein Synthesis During Infection, Purinergic regulation of T cells, Synthetic HDL_a potential sepsis therapy, Injury-Specific Activation of the Immune System, Adenosine and Oxygen Modulate Antimicrobial Defenses, Mechanism of adrenal insufficiency as a risk factor for sepsis, Maintenance of Organ Function Following Injury, Impact of Biological, Clinical, and Geographic Characteristics on Trauma and Trauma Outcomes, Role of SR-BI in LPS detoxification
OpenAlex ID: W1975622213