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.
