title: Electroconvulsive shock exposure prevents neuronal apoptosis after kainic acid-evoked status epilepticus.
abstract: In the aftermath of prolonged continuous seizure activity (status epilepticus, SE), neuronal cell death occurs in the brain regions through which the seizure propagates. The vulnerability to adrenalectomy-induced apoptotic neuronal death was recently reported to be reduced by prior exposure to repeated daily noninjurious electroconvulsive shock (ECS). The present studies identified apoptosis and apoptosis-associated gene products in the neurodegenerative response to experimentally controlled periods (1 or 2 h) of SE in the rat, and determined whether exposure to ECS can interrupt these apoptotic responses mechanisms. Internucleosomal DNA fragmentation and the presence of apoptotic-like neurons (as assessed by in situ double labeling technique) was detected in hippocampus and rhinal cortex at 24 h after SE. Under these conditions, levels of both mRNA and protein encoded by the 'death promoting' bcl-XS gene were increased in the same brain areas. Pretreatment of animals for 7 days with low intensity (minimal) ECS conferred resistance to SE-evoked neurodegeneration, as assessed histopathologically by silver staining. Associated with this neuroprotective action was a reduction in the incidence of apoptosis-like neuronal morphology and DNA fragmentation, and a prevention of the increase in Bcl-XS protein and mRNA in hippocampus and rhinal cortex. These data suggest that pre-exposure to controlled, brief noninjurious seizures decreases vulnerability to programmed neuronal cell death, that this neuroprotective action occurs upstream from Bcl-XS, and that increases in bcl-XS gene expression may serve as a sensitive indicator of neurodegeneration following SE.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA. kondrata@georgetown.edu
authors.forename: A
authors.initials: A
authors.lastname: Kondratyev
authors.forename: N
authors.initials: N
authors.lastname: Sahibzada
authors.forename: K
authors.initials: K
authors.lastname: Gale
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D053938:DNA Fragmentation; D004565:Electroconvulsive Therapy; D018728:Entorhinal Cortex / Q000473:pathology / Q000502:physiology; D018690:Excitatory Amino Acid Agonists; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D051020:bcl-X Protein
chemical_list: C494813:Bcl2l1 protein, rat; D015415:Biomarkers; D018690:Excitatory Amino Acid Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein; D007608:Kainic Acid