A chronic focal epilepsy with mossy fiber sprouting follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infant rats

Studies were conducted to characterize a chronic epileptic condition that f ollows recurrent seizures induced by intrahippocampal tetanus toxin injecti on in infancy. Wistar rat pups received a single injection of tetanus toxin in the right CA3 region on postnatal day 10. Animals were monitored for ep ileptiform activity by video electroencephalographic or visual observation during the following three to five days. Repeat evaluation six months later demonstrated interictal discharges in 79% (11 of 14) and electrographic se izures in 42% (six of 14) of adult rats with tetanus toxin-induced seizures in infancy. Five of the animals had interictal activity which occurred foc ally in either the left (n = 2) or right (n = 3) hippocampus. One animal ha d focal interictal activity independently in these regions and in the left and right cortical regions. The remaining five animals had interictal activ ity in the hippocampus and synchronously in the ipsilateral cortex or the c ontralateral hippocampus. Electrographic seizures were focal (nine of 14) o r bilateral (five of 14) in onset. The behaviors that accompanied these sei zures were quite variable. Clonic face and forelimb movements were observed in some animals. However, a significant portion of rats had electrographic seizures with no associated behavioral change. Timm staining was performed on hippocampal sections from experimental and control animals. There was a significantly greater Timm score (aberrant Timm granules) in the inner mol ecular layer of the dentate gyms in tetanus toxin-treated rats than in cont rol rats. Our findings suggest that intrahippocampal tetanus toxin injection in infan t rats results in a chronic focal epilepsy that persists for at least six m onths and is associated with aberrant mossy fiber sprouting in the dentate gyrus. The model described here contributes significantly to the evidence f or chronic effects of recurrent seizures in early life, and provides a mode l for investigation of the molecular and cellular events that contribute to the development of chronic epilepsy. (C) 1999 IBRO. Published by Elsevier Science Ltd.