The present study examined the effects of a free radical scavenger, N-tert-butyl-alfa-phenylnitrone (PBN) on lithium-pilocarpine-induced status epilepticus (SE) and its short-term consequences in rats 12 (P12) or 25 (P25) days old. PBN (2 x 100 mg/kg i.p.) was injected according to the following schedules: 1) PBN-pretreated animals received the first dose 30 min prior to pilocarpine, the second dose was given 1 min after SE onset, and 2) PBN-treated animals received the first dose of PBN 1 min after SE onset and the second one 60 min later. Paraldehyde was administered to decrease mortality. Effects of PBN were highly age-dependent. In P25 group, PBN-pretreatment increased latency to SE onset and significantly suppressed the severity of motor manifestation of SE. Both PBN pretreatment and treatment improved recovery after SE. In contrast, administration of PBN in P12 animals did not affect SE pattern or recovery after SE. Administration of PBN had no effects on the motor performance of animals 3 and 6 days after SE. Neuronal damage was examined 24 h and 7 days after SE using Fluoro-Jade B staining. Mild neuroprotective effects of PBN in hippocampal fields CA1 and CA3 occurred in P25 rats in both experimental schedules. In contrast, administration of PBN aggravated neuronal injury in the hippocampus in P12 rats. Administration of PBN to intact rats did not induce neurodegeneration in either age group.

Institute of Physiology Academy of Sciences of the Czech Republic Vídenská 1083 14220 Prague 4 Czech Republic

The Free Radical Scavenger N-Tert-Butyl-α-Phenylnitrone (PBN) Administered to Immature Rats During Status Epilepticus Alters Neurogenesis and Has Variable Effects, Both Beneficial and Detrimental, on Long-Term Outcomes