Navegando por Palavras-chave "cycloheximide"

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    Effect of long-term spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting
    (Elsevier B.V., 1999-09-01) Longo, Beatriz Monteiro [UNIFESP]; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    In a recent report we have shown that a protein synthesis inhibitor, cycloheximide (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. Under this condition animals still showed spontaneous recurrent seizures (SRS) which led us to question the role played by sprouted mossy fibers in generating those seizures. in both patients and animal models of epilepsy the relative contribution of SE (when present) and/or SRS for the development of MFS is not known. in the present study we investigated the relationship between MFS, SE and SRS, and evaluated whether the CHX-induced blockade of MFS 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 sacrificed between 8 and 10 months later, and animals that were subject to Pilo-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 CHX. Re-induction of SE or a long period of chronic seizures, were able to trigger 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. Our 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.
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    Electrophysiologic abnormalities of the hippocampus in the pilocarpine/cycloheximide model of chronic spontaneous seizures
    (Blackwell Publishing Inc, 2002-01-01) Longo, Beatriz Monteiro [UNIFESP]; Sanabria, Emilio Rafael Garrido [UNIFESP]; Gabriel, S.; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Humboldt Univ
    Purpose: Mossy fiber sprouting (MFS) and synaptic reorganization in the dentate gyrus (1)(3) is considered one of the physiopathologic mechanisms in temporal lobe epilepsy. Supragranular MFS can be blocked by cycloheximide (CHX) without interfering with the genesis of spontaneous recurrent seizures. the aim of this study was to investigate electrophysiologic properties of the hippocampus in the CHX/pilocarpine (CHX/PILO) model as compared with the conventional PILO model.Methods: in vitro electrophysiology was performed 2 months after status epilepticus (SE) induction using extracellular recordings in hippocampal slices from PILO (n = 8) and CHX/PILO animals (n = 10). Field potential responses were evoked in the CA1 and DG regions during perfusion with normal artificial cerebrospinal fluid (aCSF) and aCSF containing 3.5, 5, or 8 mM K+ without or with bicuculline added. Neo-Timm staining was used for the assessment of supragranular MFS.Results: Evoked potentials in PILO- and CHX/PILO-treated rats displayed small-amplitude polyspiking activity (epileptiform responses) in CAI and an apparently normal isolated population spike in DG. More important, PILO and CHX/PILO animals did not differ regarding electrophysiologic abnormalities, even under high K+ or high K+/bicuculline. Analysis of the neo-Timm staining revealed strong supragranular MFS in PILO-injected rats and significantly less staining in CHX/PILO rats. Thus, occurrence of abnormal stimulus responses and high K+- or high K+/bicuculline-induced epileptiform activities did not depend on the degree of MFS.Conclusions: We therefore suggest that other mechanisms such as anomalous intrinsic bursting and disinhibition rather than MFS might account for the increased hippocampal hyperexcitability in this model.
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    Sprouting of mossy fibers and the vacating of postsynaptic targets in the inner molecular layer of the dentate gyrus
    (Elsevier B.V., 2003-05-01) Longo, B.; Covolan, Luciene [UNIFESP]; Chadi, G.; Mello, LEAM; Universidade Federal de São Paulo (UNIFESP); UNIBAN; Universidade de São Paulo (USP)
    Aberrant mossy fiber sprouting, which presumably results from hilar mossy cell death after status epilepticus (SE), is a frequently studied feature of temporal lobe epilepsy. Although mossy fiber sprouting can be suppressed by the protein synthesis inhibitor cycloheximide, spontaneous seizures remain unaltered. We have investigated the mechanisms underlying the ability of cycloheximide to block SE-induced mossy fiber sprouting in the inner molecular layer of dentate gyrus (IML). Pilocarpine-induced SE in the presence of cycloheximide resulted in a reduced number of injured hilar cells compared to rats not pretreated with cycloheximide. Presumed mossy cells, identified by calcitonin gene related peptide (CGRP) immunohistochemistry, were not significantly reduced in either group 60 days after SE. Whereas controls had a strong band of CGRP-positive fibers (putative mossy cell axons) and no neo-Timm stained fibers in the IML, pilocarpine-treated rats had no CGRP fibers and strong neo-Timm staining. Cycloheximide-pilocarpine-treated animals, in contrast, had CGRP and neo-Timm staining similar to controls. Cycloheximide might protect hilar CGRP-positive cells during SE. and, by allowing those cells to retain their normal axonal projection, prevent mossy fiber sprouting. the recently suggested irritable mossy cell hypothesis relies on the survival of mossy cells for network hyperexcitability. We hypothesized that CGRP may be a marker for a subpopulation of relatively resistant mossy cells in rats, which, if they survive injury, may become irritable and contribute to hyperexcitability. We suggest that cycloheximide prevents SE-induced mossy fiber sprouting by preventing the loss of hilar CGRP-positive cells (putative mossy cells). (C) 2003 Elsevier Science (USA). All rights reserved.