This book sets out to explain the clinically relevant basic mechanisms of excitotoxic neuronal death, which in the adult mammalian brain is morphologically necrotic, not apoptotic, and which involve caspase-independent mechanisms of programmed cell death.
This book is the result of a convergence of scientific information regarding mechanisms that produce acute nerve cell death in the brain. Although seemingly disparate, stroke, brain and spinal cord trauma, coma from a low serum glucose concentration (hypoglycemia), and prolonged epileptic seizures have in common the inciting factor of excitotoxicity, the activation of a specific subtype of glutamate receptor by an elevated extracellular glutamate concentration that results in an excessive influx of calcium into nerve cells. The high calcium concentration in nerve cells activates several enzymes that are responsible for degradation of cytoplasmic proteins and cleavage of nuclear DNA, resulting in nerve cell death. The high calcium concentration also interferes with mitochondrial respiration, with the resultant production of free radicals that damage cellular membranes and nuclear DNA. Understanding the biochemical pathways that produce nerve cell death is the first step toward devising an effective neuroprotective strategy, the ultimate goal.
Acute Neuronal Injury will be useful to neuroscientists and general cell biologists interested in cell death. The book will also be helpful to clinically oriented neuroscientists, including neurologists, neurosurgeons and psychiatrists.
About the Editor:
Dr. Denson Fujikawa is an Adjunct Professor of Neurology at the David Geffen School of Medicine at UCLA, a member of the Brain Research Institute at UCLA and a Sta
ff Neurologist at the Department of Veterans Affairs Greater Los Angeles Healthcare System. His interest in mechanisms of nerve cell death in the brain began during a two-year epilepsy research fellowship with Dr. Claude Wasterlain, from 1981 to 1983. He is a Fellow of the American Academy of Neurology and is a member of the American Epilepsy Society, American Neurological Association, International Society for Cerebral Blood Flow and Metabolism, and the Society for Neuroscience.
INTRODUCTION: Programmed mechanisms and the clinical spectrum of excitotoxic neuronal death (Denson G. Fujikawa).- PART 1: Caspase-independent programmed cell death: general considerations.- Chapter 1: Caspase-independent cell death mechanisms in simple animal models (Matthias Rieckher and Nektarios Tavernarakis).- Chapter 2: Programmed necrosis: a 'new' cell death outcome for injured adult neurons? (Slavica Krantic and Santos A. Susin).- Chapter 3: Age-dependence of neuronal apoptosis and of caspase activation (Denson G. Fujikawa).- Chapter 4: Excitotoxic programmed cell death involves caspase-independent mechanisms (Ho Chul Kang, Ted M. Dawson and Valina L. Dawson).- PART 2: Focal Cerebral ischemia.- Chapter 5: Apoptosis-inducing factor translocation to nuclei in focal cerebral ischemia (Carsten Culmsee and Nicholas Plesnila).- Chapter 6: The role of poly(ADP-ribose) polymerase-1 (PARP-1) activation in focal cerebral ischemia (Giuseppe Faraco and Alberto Chiarugi).- PART 3: Transient Global Ischemia.- Chapter 7: Transient global cerebral ischemia produces necrotic, not apoptotic neurons (Frederick Colbourne and Roland Auer).- Chapter 8: Apoptosis-inducing factor translocation to nuclei after transient global ischemia (Can Liu, Armando P. Signore, Guodong Cao and Jun Chen).- Chapter 9: Role of µ-calpain I and lysosomal cathepsins in hippocampal neuronal necrosis after transient global ischemia in primates (Anton B. Tonchev and Tetsumori Yamashima).- PART 4: Traumatic central nervous system (CNS) injury.- Chapter 10: Mitochondrial damage in traumatic CNS injury (Laurie M. Davis and Patrick G. Sullivan).- Chapter 11: Programmed mechanisms in traumatic CNS injury (Bogdan A. Stoica and Alan I. Faden).- PART 5: Hypoglycemic neuronal death.- Chapter 12: Hypoglycemic neuronal death: morphological considerations (tentative title pending receipt of manuscript; Roland Auer).- Chapter 13:The role of poly(ADP-ribose) polymerase-1 (PARP-1) in hypoglycemic neuronal death (tentative title pending receipt of manuscript; Sang Won Suh and Raymond A. Swanson).- PART 6: Seizure-induced neuronal death.- Chapter 14: p53 activation is necessary in seizure-induced neuronal death (Zhiquin Tan and Steven S. Schreiber).- Chapter 15: DNA damage and repair in the brain: implications for seizure-induced neuronal injury, endangerment, and neuroprotection (Samantha L. Crowe and Alexei D. Kondratyev).- Chapter 16: Activation of caspase-independent programmed pathways in seizure-induced neuronal necrosis (Denson G. Fujikawa).- CONCLUDING REMARKS (Denson G. Fujikawa)
"This is an outstanding book concerning the molecular and cellular mechanisms of trauma and ischemia in the mammalian brain. ... I recommend his book to neurophysiologists, neurologists, and neurosurgeons." (Joseph J. Grenier, Amazon.com, September, 2015)
Über den Autor
Dr. Denson Fujikawa is an Adjunct Professor of Neurology at the David Geffen School of Medicine at UCLA, a member of the Brain Research Institute at UCLA and a Staff Neurologist at the Department of Veterans Affairs Greater Los Angeles Healthcare System. His interest in mechanisms of nerve cell death in the brain began during a two-year epilepsy research fellowship with Dr. Claude Wasterlain, from 1981 to 1983. He is a Fellow of the American Academy of Neurology and is a member of the American Epilepsy Society, American Neurological Association, International Society for Cerebral Blood Flow and Metabolism and the Society for Neuroscience.
Denson G. Fujikawa 2+ In the early 1980s it was recognized that excessive Ca influx, presumably through 2+ 2+ voltage-gated Ca channels, with a resultant increase in intracellular Ca , was associated with neuronal death from cerebral ischemia, hypoglycemia, and status epilepticus (Siejö 1981). Calcium activation of phospholipases, with arachidonic acid accumulation and its oxidation, generating free radicals, was thought to be a potential mechanism by which neuronal damage occurs. In cerebral ischemia and 2+ hypoglycemia, energy failure was thought to be the reason for excessive Ca influx, whereas in status epilepticus it was thought that repetitive depolarizations were responsible (Siejö 1981). Meanwhile, John Olney found that monosodium glutamate, the food additive, when given to immature rats, was associated with neuronal degeneration in the arcuate nucleus of the hypothalamus, which lacks a blood-brain barrier (Olney 1969). He followed up this observation with a series of observations in the 1970s that administration of kainic acid, which we now know activates the GluR5-7 subtypes of glutamate receptor, and other glutamate analogues, caused not only post-synaptic cytoplasmic swelling, but also dark-cell degeneration of neurons, when viewed by electron microscopy (Olney 1971; Olney et al. 1974).
Presents the most up-to-date information on all aspects of excitotoxic neuronal death