title: Morphologic study of neuronal death, glial activation, and progenitor cell division in the hippocampus of rat models of epilepsy.
abstract: OBJECTIVE
  To clarify the relationship of neuronal death to cellular responses, we studied neuronal death as well as reactions of glia and progenitor cells in the hippocampus of two rat models of epilepsy.
  
  
  METHODS
  Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neuronal degeneration was assessed by in situ DNA fragmentation analysis. Reactions of glial cells were studied by immunohistochemistry. Progenitor cell division was evaluated using the bromodeoxyuridine (BrdU) labeling method.
  
  
  RESULTS
  DNA fragmentation and reactive microglia were observed in the CA1, CA3, and hilus region for 24 h to 4 weeks after KA injection, but not detected in the kindling model. Reactive astrocytes and enhancement of progenitor cell division were seen in both animal models. The number of BrdU-positive cells began to increase on day 3 after KA injection, peaked on day 5, and returned to baseline on day 10. After kindling, the number of BrdU-positive cells began to increase after five consecutive experience of stage I seizures.
  
  
  CONCLUSIONS
  These observations show that neuronal degeneration is not necessary for triggering the upregulation. Microglial activation is closely related to the neuronal death process induced by KA.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta, Otsu, Japan. kinchan@belle.shiga-med.ac.jp
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bellier
authors.forename: Masami
authors.initials: M
authors.lastname: Park
authors.forename: Petra
authors.initials: P
authors.lastname: Minnasch
authors.forename: Shuji
authors.initials: S
authors.lastname: Uemura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisano
authors.forename: Mika
authors.initials: M
authors.lastname: Iwami
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Aimi
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuhara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage; D016923:Cell Death; D002455:Cell Division; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004827:Epilepsy / Q000473:pathology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D007696:Kindling, Neurologic; D008297:Male; D017628:Microglia / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D001973:Bromodeoxyuridine; D007608:Kainic Acid