Activation of Caspase-Independent Programmed Pathways in Seizure-Induced Neuronal Necrosis

  • Denson G. Fujikawa


Our current concept of how prolonged epileptic seizures (status epilepticus, or SE) kill neurons originated in the 1970s from the pioneering work done by John Olney and associates. Olney reported in 1969 that monosodium glutamate killed neurons in the hypothalamic arcuate nucleus, a region that lacks a blood–brain barrier (Olney 1969). Subsequently, Olney and associates found that administration of glutamate (GLU), the most abundant excitatory neurotransmitter in the brain, killed hypothalamic neurons in the infant mouse (Olney 1971), and that systemic administration of a GLU analogue, kainic acid (KA) to the adult rodent resulted in SE and neuronal death (Olney et al. 1974). In 1985, Olney put forth his excitotoxic hypothesis as it applies to SE (Olney 1985). This hypothesis, which states that excessive presynaptic GLU release results in the death of postsynaptic neurons, has proved to be remarkably robust, and is applicable to a wide variety of acute neuronal insults, as mentioned in the Introduction.


Status Epilepticus Kainic Acid Piriform Cortex Monosodium Glutamate Cellular Necrosis 
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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Neurology DepartmentVA Greater Los Angeles Healthcare SystemNorth HillsUSA
  2. 2.Department of Neurology and Brain Research InstituteDavid Geffen School of Medicine, University of CaliforniaLos AngelesUSA

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