Document Detail

New insights on brain stem death: from bedside to bench.
MedLine Citation:
PMID:  16376477     Owner:  NLM     Status:  MEDLINE    
As much as brain stem death is currently the clinical definition of death in many countries and is a phenomenon of paramount medical importance, there is a dearth of information on its mechanistic underpinnings. A majority of the clinical studies are concerned only with methods to determine brain stem death. Whereas a vast amount of information is available on the cellular and molecular mechanisms of cell death, rarely are these studies directed specifically towards the understanding of brain stem death. This review presents a framework for translational research on brain stem death that is based on systematically coordinated clinical and laboratory efforts that center on this phenomenon. It begins with the identification of a novel clinical marker from patients that is related specifically to brain stem death. After realizing that this "life-and-death" signal is related to the functional integrity of the brain stem, its origin is traced to the rostral ventrolateral medulla (RVLM). Subsequent laboratory studies on this neural substrate in animal models of brain stem death provide credence to the notion that both "pro-life" and "pro-death" programs are at work during the progression towards death. Those programs (mitochondrial functions, nitric oxide, peroxynitrite, superoxide anion, coenzyme Q10, heat shock proteins and ubiquitin-proteasome system) hitherto identified from the RVLM are presented, along with their cellular and molecular mechanisms. It is proposed that outcome of the interplay between the "pro-life" and "pro-death" programs (dying) in this neural substrate determines the final fate of the individual (being dead). Thus, identification of additional programs in the RVLM and delineation of their regulatory mechanisms should shed new lights on future directions for clinical management of life-and-death.
Julie Y H Chan; Alice Y W Chang; Samuel H H Chan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2005-12-22
Journal Detail:
Title:  Progress in neurobiology     Volume:  77     ISSN:  0301-0082     ISO Abbreviation:  Prog. Neurobiol.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2006-01-09     Completed Date:  2006-03-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370121     Medline TA:  Prog Neurobiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  396-425     Citation Subset:  IM    
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81346, Taiwan, ROC.
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MeSH Terms
Blood Pressure / physiology
Brain Death*
Brain Stem* / anatomy & histology,  physiology
Cardiovascular Physiological Phenomena
Heat-Shock Proteins / metabolism
Isoenzymes / metabolism
Mitochondria / metabolism
Nitric Oxide / metabolism
Nitric Oxide Synthase / metabolism
Proteasome Endopeptidase Complex / metabolism
Signal Transduction / physiology
Ubiquitin / metabolism
Vasomotor System / physiology
Reg. No./Substance:
0/Heat-Shock Proteins; 0/Isoenzymes; 0/Ubiquitin; 10102-43-9/Nitric Oxide; EC Oxide Synthase; EC Endopeptidase Complex

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