The duration of sustained convulsive seizures determines the pattern of hippocampal neurogenesis and the development of spontaneous epilepsy in rats.
The duration of sustained seizures (SS) plays a crucial role in the occurrence of spontaneous recurrent seizures (SRS) in experimental animals. We tested whether rats with varying durations of initial convulsive SS exhibited differential neurogenesis patterns in the hippocampal dentate gyrus that may be related to subsequent epileptogenesis. Sprague-Dawley rats with pilocarpine-induced convulsive SS were divided into short SS (30 min) and long SS (2 h) groups. Their behavior was monitored to identify convulsive SRS. From 1 to 28 days post-SS, cell proliferation was evaluated by 5'-bromo-2'-deoxyuridine (BrdU) labeling and immature neuroblasts in the dentate gyrus were identified by doublecortin immunohistochemistry. Convulsive SRS was detected in 8 out of the 9 long SS rats, but not in the 9 short SS rats. During day 1-3, proliferative cells were diffusely localized throughout the hippocampus in the long SS rats but were primarily confined within the subgranular zone in the short SS rats. Within the subgranular zone, a significant increase in the number of BrdU-positive cells was found at days 3 and 7 after the long SS and on day 1 after the short SS. Notably, abnormal dendritic outgrowth and hilar-ectopic localization of doublecortin-positive cells were present in the long SS rats. In conclusion, aberrant hippocampal neurogenesis following long SS may contribute to the development of SRS.
Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
Yu-Wen
YW
Hung
Ding-I
DI
Yang
Pei-Yu
PY
Huang
Tzong-Shyuan
TS
Lee
Terry B J
TB
Kuo
Chun-Hing
CH
Yiu
Yang-Hsin
YH
Shih
Yung-Yang
YY
Lin
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010862:Pilocarpine; D001973:Bromodeoxyuridine