Morphologic study of neuronal death, glial activation, and progenitor cell division in the hippocampus of rat models of epilepsy.
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.
Tooyama
Ikuo
I
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta, Otsu, Japan. kinchan@belle.shiga-med.ac.jp
Bellier
Jean-Pierre
JP
Park
Masami
M
Minnasch
Petra
P
Uemura
Shuji
S
Hisano
Tadashi
T
Iwami
Mika
M
Aimi
Yoshinari
Y
Yasuhara
Osamu
O
Kimura
Hiroshi
H
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
D018690:Excitatory Amino Acid Agonists; D001973:Bromodeoxyuridine; D007608:Kainic Acid