Abstracts

Neurogenesis of dentate granule cells of the hippocampal formation continues well into the postnatal period in primates and in the rat at least, occurs throughout adult life. Furthermore, epileptic seizures have been shown to stimulate the proliferation rate of granule cell progenitors in the adult rat brain. In the present study, we investigated whether the proliferation of granule cell progenitors is increased in mice in a model of kainic acid (KA)-induced seizure, by using systemic bromodeoxyuridine (BrdU) injections to label dividing cells. Ten male ICR mice were dived into two equal groups. Seizures were chemically induced by intraperitoneal injection of KA (30 mg/kg). Seizure severity was evaluated using a seizure behavior grading system: 0, no response; 1, front or hid limb pawing, staring; 2, rearing, staring, nodding, bilateral pawing; 3, rearing, staring, nodding, bilateral pawing, jumping, wobbling, falling; 4, status epilepticus or death. The mice injected with equal volume of normal saline were used as controls. BrdU (50 mg/kg) was then subsequently administered intraperitoneally for 6 consecutive days, starting at 24 hours after KA or saline injection. All mice were sacrificed 24 hours after the last BrdU injection, and the brains were removed for tissue fixation and immunohistochemistry. BrdU-labeled cells in the combined hippocampal dentate gyrus and hilar regions were counted in every seventh sections in a series of 30 [mu]m sagittal sections (210 [mu]m apart) covering the complete left and right hippocampi. After KA administration, every seizure behavior was grade 2 or more. BrdU-labeled cells increased significantly (p [lt] 0.00001) after KA-induced seizures (83.38 [plusmn] 44.33) compared to controls (35.61 [plusmn] 17.87). Most of newborn cells migrated into the granule cell layer from the subgranular zone after KA-induced seizures. In this study, quantitative analysis of BrdU labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells after KA-induced seizures in mice. Our results suggest that increased neurogenesis may be a general response to seizure activity. The functional significance of dentate granule cell neurogenesis in epileptogenesis still remains unknown and should be investigated. (Supported by a grant of the Korea Health 21 R[amp]D Project, Ministry of Health [amp] Welfare, Republic of Korea. (02-PJ1-PG10-21301-0001))