Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures

Abstract

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5–10 rats, KA caused generalized tonic-clonic (‘swimming’) seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20–30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20–30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20–30 rats. CA3 lesions were seen in P20–60 rats with and without SRS, but not in P5–10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.