New insights on brain stem death: From bedside to bench

Julie Y.H. Chan, Ya-Wen Zhang, Samuel H.H. Chan

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)396-425
Number of pages30
JournalProgress in Neurobiology
Volume77
Issue number6
DOIs
Publication statusPublished - 2005 Dec 1

Fingerprint

Brain Death
Brain Stem
coenzyme Q10
Peroxynitrous Acid
Translational Medical Research
Proteasome Endopeptidase Complex
Ubiquitin
Heat-Shock Proteins
Superoxides
Nitric Oxide
Cell Death
Animal Models
Biomarkers
Light

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Chan, Julie Y.H. ; Zhang, Ya-Wen ; Chan, Samuel H.H. / New insights on brain stem death : From bedside to bench. In: Progress in Neurobiology. 2005 ; Vol. 77, No. 6. pp. 396-425.
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New insights on brain stem death : From bedside to bench. / Chan, Julie Y.H.; Zhang, Ya-Wen; Chan, Samuel H.H.

In: Progress in Neurobiology, Vol. 77, No. 6, 01.12.2005, p. 396-425.

Research output: Contribution to journalReview article

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