Translational Research in Biomedicine
1 primary work
Book 8
A Chronicle of Three Decades of Search for Its Cellular and Molecular Mechanisms Brain-based account of death has been the subject of continuous debate since its introduction in 1968 in the Harvard Report. Most of the deliberations concern the pros-and-cons of methods, guidelines, and policies for the determination of brain death, or the legal, social, ethical, cultural and religious implications.Studies that direct specifically on the cellular and molecular mechanisms of brain death, on the other hand, remain dearth. This book chronicles the first comprehensive effort to fill this knowledge void. The 30-year journey of the author and his colleagues began with a serendipitous discovery of a novel biomarker that is related to the functional integrity of the brain stem and inevitably disappears in patients confirmed of brain death. That this life-and-death signal undergoes waxing and waning in animal models suggests that progression towards brain stem death encompasses exhibition of pro-life and pro-death phases in succession. Searching systematically from a brain stem neural substrate where this biomarker originates revealed that it is the outcome of interplays between pro-life and pro-death cellular and molecular programs (nitric oxide synthases, mitochondrial bioenergetics, heat shock proteins, hypoxia-inducible factor-1, heme oxygenase-1, ubiquitin-proteasome system, sumoylation or PTEN/PI3K/Akt/NF- B) and transition from oxidative stress to nitrosative stress that determine the final fate of the individual. Given that brain stem death is irreversible, this book provides mechanistical hints for the development of strategies that prevent critically ill patients to move from pro-life phase to pro-death phase.This book is particularly recommended to specialists in critical care medicine, neurology, transplantation, and translational medicine.