Role of kinin B1 and B2 receptors in the development of pilocarpine model of epilepsy

Abstract

The tissue sclerosis found in epilepsy of limbic origin is characterized by shrunken gliotic hippocampus, granule cell loss in the dentate gyrus and extensive pyramidal cell loss in Ammon's horn. Evidence has indicated that sprouting of dentate granule cell axons into the inner molecular layer of the dentate gyrus is related to hyperexcitability. Trying to understand the role of kinin B1 and B2 receptors in the physiopathology of temporal lobe epilepsy (TLE), the present work was delineated to study the development of the epilepsy model induced by pilocarpine in B1 and B2 knockout mice (B1KO and B2KO, respectively). Behavior parameters, cell death and mossy fiber sprouting were analyzed. B1KO mice showed increased latency for the first seizure, associated to a decreased frequency of spontaneous seizures, when compared with wild-type mice. in addition, B1KO mice showed less cell death in all hippocampal formation associated to a reduced grade of mossy fiber sprouting. Furthermore, B2KO mice presented minor duration of the silent period and an increased frequency of spontaneous seizures, when compared with wild-type mice. B2KO and their control lineage showed similar pattern of cell death in the hippocampus, which was very intense when compared with saline-treated animals. the mossy fiber sprouting was also increased in B2KO mice, when compared to wild-type mice and saline-treated animals. Taken together, these data suggest a deleterious effect for kinin B I receptor and a protective effect for kinin B2 receptor during the development of the temporal lobe epilepsy. (C) 2004 Elsevier B.V. All rights reserved.