Granule cell neurogenesis after status epilepticus in the immature rat brain

Purpose: Several experimental paradigms of seizure induction that produce e pilepsy as a consequence have been shown to be associated with the prolifer ation of dentate granule cells. In developing animals, the acute sequela of hilar damage and the chronic sequelae of spontaneous seizures and mossy fi ber synaptic reorganization, in response to status epilepticus, occur in an age-dependent manner. We investigated seizure-induced granule cell neuroge nesis in developing rat pups to study the association between hilar injury, granule cell neurogenesis, and epilepsy. Methods: Rat pups of 2 and 3 weeks postnatal age were subjected to lithium- pilocarpine status epilepticus (LiPC SE). Rats were given bromodeoxyuridine (BrdU; 50 mg/kg intraperitoneal) twice daily for 4 days beginning 3 days a fter SE to label dividing cells. Routine immunocytochemistry and quantifica tion of BrdU labeling image analysis were performed. Results were compared with previously reported data on cellular injury, mossy fiber sprouting, an d spontaneous seizures in rat pups of these ages after LiPC SE. Results: In 3-week-old pups, which demonstrate SE-induced hilar damage and develop spontaneous seizures accompanied by mossy fiber sprouting, the BrdU -immunoreactive area (percent) in the subgranular proliferative zone increa sed to 10.6 +/- 2.5 compared with 1.4 +/- 0.5 in the control animals (p < 0 .05). The 2-week-old animals, which show neither hilar damage nor sprouting and rarely develop spontaneous seizures, also showed a comparable extent o f SE-induced neurogenesis [8.0 +/- 1.4 (LiPC SE) versus 0.4 +/- 0.2 (contro l), p < 0.05]. Conclusions: Seizure-induced granule cell neurogenesis does not appear to b e a function of seizure-induced hilar cellular damage. Granule cell neuroge nesis induced by SE does not determine epileptogenesis in the developing ra t.