Long-term effects of intrahippocampal kainic acid injection in rats: A method for inducing spontaneous recurrent seizures

Abstract

Kainic acid (KA) is known as a powerful convulsant and neurotixic agent. When intracerebrally administered it causes repetitive seizures for about 1 or 2 days and brain damage both locally and in several remote brain regions. In the present paper the longterm effects of intrahippocampal KA administration are reported. Doses from 0.1 to 3.0 μg of KA were injected in the right hippocampus of Wistar rats and both the behaviour and EEG were observed during a period of about 3 months. Following KA doses of 0.8–2.0 μg, 4 distinct phases were observed: (1) acute phase which lasted 1–2 days and corresponded to the pattern of repetitive seizures as already described; (2) silent phase (5–21 days) which was characterized by a progressive return to apparently normal EEG and behaviour, except for some aggressive behaviour in those animals receiving the highest doses; (3) phase of spontaneous recurrent seizures (these seizures started 6–22 days after KA injections and were mostly triggered upon handling and recurred approximately 2 times by day for about 30 days; usually they resembled the amygdaloid kindled seizures); and (4) post-seizure phase where no more seizures were observed but significant spiking activity in the amygdala recordings could be seen. Animals receiving KA doses of 0.1–0.4 μg did not evolve beyond the acute phase whereas those receiving 3.0 μg died during this first phase. Neuropathological examination revealed dose-dependent alterations. These serial events offer a new method to induce spontaneous recurrent seizures with brain damage.