Main description:

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 (Siejo 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 (Siejo 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).

Contents:

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 -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)