Seizure-induced neuronal death in the immature brain.
The response of the developing brain to epileptic seizures and to status epilepticus is highly age-specific. Neonates with their low cerebral metabolic rate and fragmentary neuronal networks can tolerate relatively prolonged seizures without suffering massive cell death, but severe seizures in experimental animals inhibit brain growth, modify neuronal circuits, and can lead to behavioral deficits and to increases in neuronal excitability. Past infancy, the developing brain is characterized by high metabolic rate, exuberant neuronal and synaptic networks and overexpression of receptors and enzymes involved in excitotxic mechanisms. The outcome of seizures is highly model-dependent. Status epilepticus may produce massive neuronal death, behavioral deficits, synaptic reorganization and chronic epilepsy in some models, little damage in others. Long-term consequences are also highly age- and model-dependent. However, we now have some models which reliably lead to spontaneous seizures and chronic epilepsy in the vast majority of animals, demonstrating that seizure-induced epileptogenesis can occur in the developing brain. The mode cell death from status epilepticus is largely (but not exclusively) necrotic in adults, while the incidence of apoptosis increases at younger ages. Seizure-induced necrosis has many of the biochemical features of apoptosis, with early cytochrome release from mitochondria and capase activation. We speculate that this form of necrosis is associated with seizure-induced energy failure.
Wasterlain
Claude G
CG
Epilepsy Research Laboratory, VA Greater Los Angeles Healthcare System, Department of Neurology Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA. wasterla@ucla.edu
Niquet
Jerome
J
Thompson
Kerry W
KW
Baldwin
Roger
R
Liu
Hanato
H
Sankar
R
R
Mazarati
Andrey M
AM
Naylor
David
D
Katsumori
Hiroshi
H
Suchomelova
Lucie
L
Shirasaka
Yukioyoshi
Y
D000375:Aging; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D016923:Cell Death; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D008959:Models, Neurological; D009474:Neurons / Q000473:pathology*; D012640:Seizures / Q000473:pathology*; D013226:Status Epilepticus / Q000473:pathology*