Effect of long-term spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting

In a recent report we have shown that a protein synthesis inhibitor, cycloh eximide (CHX), is able to block the mossy fiber sprouting (MFS) that would otherwise be triggered by pilocarpine (Pilo)-induced status epilepticus (SE ), and also gives relative protection against hippocampal neuronal death. U nder this condition animals still showed spontaneous recurrent seizures (SR S) which led us to question the role played by sprouted mossy fibers in gen erating those seizures. In both patients and animal models of epilepsy the relative contribution of SE (when present) and/or SRS for the development o f MFS is not known. In the present study we investigated the relationship b etween MFS, SE and SRS, and evaluated whether the CHX-induced blockade of M FS was transient or permanent in nature. We performed a chronic study which included animals subject to Pilo-induced SE in the presence of CHX and sac rificed between 8 and 10 months later, and animals that were subject to Pil o-induced SE in the presence of CHX and underwent a reinduction of SE with Pilo, 45 days after the first induction, but this time in the absence of CH X. Re-induction of SE or a long period of chronic seizures, were able to tr igger supragranular MFS even in animals where the first (or only) SE event was triggered in the presence of CHX. MFS did not show any association with the frequency of SRS, and thus seemed to depend more critically on time. O ur current findings allow us to suggest that MFS are neither the cause nor the consequence of SRS in the pilocarpine model. (C) 1999 Elsevier Science B.V. All rights reserved.