Carbamazepine inhibits angiotensin I-converting enzyme, linking it to the pathogenesis of temporal lobe epilepsy

We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin–angiotensin and kallikrein–kinin systems

Tyrosine phosphorylation is increased in the rat hippocampus during the status epilepticus induced by pilocarpine

Phosphorylation of tyrosine residue in proteins is an important modulatory process for membrane transduction and cell signaling and for several cellular functions. the concentration and distribution of phosphotyrosine proteins were analyzed in the hippocampi of rats in the model of epilepsy induced by pilocarpine using Western blotting and immunohistochemistry. the concentration of several phosphotyrosine proteins increased during status epilepticus, During the seizure-free period and the chronic period of this epilepsy model, the hippocampi of rats did not exhibit changes in the expression of these proteins. Immunohistochemistry showed an increased immunoreactivity throughout the hippocampal formation of rats 1 h after states epilepticus that was acutely induced by pilocarpine, Animals killed after 3 h of states epilepticus showed an increased expression of phosphotyrosine in the hippocampal hilus and CA3 regions. After 5 h of states epilepticus, phosphotyrosine immunoreactivity persisted only in the CA3 region. After 12 h of status epileptices, the hippocampal formation exhibited a normal phosphotyrosine immunostaining, showing that the increased expression of these proteins is related to the acute phase and that several intracellular events could undergo modifications during the status epilepticus induced by pilocarpine, (C) 1998 Elsevier Science Inc.Universidade Federal de São Paulo, Disciplina Neurol Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Bioquim, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Expt, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Bioquim, BR-04023900 São Paulo, BrazilWeb of Scienc

Growth-associated phosphoprotein expression is increased in the supragranular regions of the dentate gyrus following pilocarpine-induced seizures in rats

Neuroplasticity has been investigated considering the neuronal growth-associated phosphoprotein as a marker of neuronal adaptive capabilities. in the present work, studying the hippocampal reorganization observed in the epilepsy model induced by pilocarpine, we carried out quantitative western blotting associated with immunohistochemistry to determine the distribution of growth-associated phosphoprotein in the hippocampus of rats in acute, silent and chronic periods of this epilepsy model. the fibers and punctate elements from the inner molecular layer of the dentate gyrus were strongly immunostained in animals killed 5 h after status epilepticus, compared with the same region in control animals. Rats presenting partial seizures showed no alterations in the immunostaining pattern compared with saline-treated animals. the hippocampal dentate gyrus of animals during the seizure-free period and presenting spontaneous recurrent seizures was also characterized by strong growth-associated phosphoprotein immunostaining of fibers and punctate elements in the inner molecular layer, contrasting with the control group. As determined by western blotting analysis, growth-associated phosphoprotein levels increased following status epilepticus and remained elevated at the later time-points, both during the silent period and during the period of chronic recurring seizures. Pilocarpine-treated animals, which did not develop status epilepticus, showed no change in growth-associated phosphoprotein levels, indicating that status epilepticus is important to induce growth-associated phosphoprotein overexpression.The measurement of this overexpression could represent one of the early signals of hippocampal reorganization due to status epilepticus-induced damage. (C) 1999 IBRO. Published by Elsevier B.V.Escola Paulista Med, UNIFESP, Disciplina Neurol Expt, BR-04023900 São Paulo, SP, BrazilEscola Paulista Med, UNIFESP, Disciplina Bioquim, BR-04023900 São Paulo, SP, BrazilEscola Paulista Med, UNIFESP, Disciplina Neurol Expt, BR-04023900 São Paulo, SP, BrazilEscola Paulista Med, UNIFESP, Disciplina Bioquim, BR-04023900 São Paulo, SP, BrazilWeb of Scienc

Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus

Systemic administration of pilocarpine (PILO) in adult rat produces acute limbic seizures leading to states epilepticus. Recent studies have shown the activation of mitogen-activated protein kinase (MAPK) cascades during experimentally induced seizures. MAPK activation may be triggered by glutamatergic stimulation and may play a key role in signal transduction pathways, in the present study, immunocytochemistry was used to analyze the spatiotemporal distribution pattern of the MARK protein and its active form (A-MAPK) following PILO-induced status epilepticus, MAPK and A-MARK immunoreactivities exhibited different patterns of distribution in the brain of normal and epileptic rats. the saline-treated rats, as well as the animals that received PILO but did not evolve to status epilepticus, showed a weak but selective MAPK immunoreactivity, detected in the hippocampal pyramidal neurons, dentate gyrus, hilus, CA3, CA1, and entorhinal, piriform, and cingulate cortices. A-MARK immunoreactivity was instead observed only in neurites of the CA3 and hilus and in cells of the entorhinal and piriform cortices, in PILO-treated rats, between 30 and 60 min after states epilepticus there was an increase of the immunoreactivity to both antibodies, which were differently distributed throughout several structures of the limbic system. the immunostaining showed a slight decrease after 5 h of states epilepticus, However, MARK and A-MARK immunopositivities decreased markedly after 12 h of states epilepticus, returning almost to the basal expression. These findings are consistent with a spatial and time-dependent MAPK expression in selected limbic structures, and its activation could represent an initial trigger for neuronal modifications that may take part in the mechanism underlying acute epileptogenesis and in longlasting neuropathological changes of the PILO model of epilepsy. (C) 1998 Elsevier Science Inc.UNIFESP, EPM, Dept Expt Neurol, São Paulo, BrazilUNIFESP, EPM, Dept Biochem, São Paulo, BrazilUNIFESP, EPM, Dept Expt Neurol, São Paulo, BrazilUNIFESP, EPM, Dept Biochem, São Paulo, BrazilWeb of Scienc

Calcium homeostasis and temporal lobe epilepsy

Univ Fed Sao Paulo, UNIFESP, Dept Bioquim, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Neurol & Neurocirurg, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Bioquim, BR-04023900 Sao Paulo, BrazilUniv Fed Sao Paulo, UNIFESP, Dept Neurol & Neurocirurg, BR-04023900 Sao Paulo, BrazilWeb of Scienc

Expression of nestin in the hippocampal submitted to the pilocarpine model formation of rats of epilepsy

Nestin is an embryonic intermediate filament component protein, transiently expressed by the immediate precursor cells of neurons and glia, during brain development. We studied the nestin distribution in the hippocampal formation of rats submitted to pilocarpine model of epilepsy. Animals were studied during the acute, silent and chronic phases. Rats from control and acute groups presented absence of nestin-immunoreactivity (IR) in the hippocampal cells. in contrast, cells from this region presented strong nestin IR during the silent phase (3 and 7 days after status epilepticus (SE) onset), disappearing 14 days after SE. Nestin IR cells were scattered expressed in all hippocampal formation during the chronic phase. Almost all nestin IR cells exhibited glial fibrillary acidic protein (GFAP), which seems to revert to a more primitive glial form, as part of an adaptive response, transiently re-expressing phenotypic features typical of earlier stages of glial development. the re-expression of this developmental protein in the damaged cerebral tissue suggests that nestin may play an important role in the reconstruction of the glial cytoskeleton and/or remodeling events occurring in the pilocarpine model of epilepsy. Understanding how astrocytes influence network function in the injured hippocampus may, therefore, provide insight into epileptogenic mechanisms. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.UNIFESP, Lab Neurol Expt, BR-04042003 São Paulo, BrazilUniv Mogi Cruzes, NPT UMC, Lab Neurociencias Nucl Pesquisas Tecnol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUNIFESP, Lab Neurol Expt, BR-04042003 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc