Repositório Institucional - Unifesp :: Navegando por Palavras-chave "pilocarpine"

Navegando por Palavras-chave "pilocarpine"

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Acute or chronic effects of cannabinoids on spontaneous or pharmacologically induced yawning in rats
(Elsevier B.V., 2002-12-01) Nakamura-Palacios, E. M.; Bueno, OFA; Takahashi, R. N.; Tufik, S.; Fed Univ Espirito Santo; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Santa Catarina (UFSC)
Yawning is a reflex or event that is not fully understood. It is controlled by many neurotransmitters and neuropeptides and can be induced pharmacologically by cholinergic or dopaminergic agonists. Amongst their many actions, cannabinoids acting on cannabinoid (CB1 or CB2) receptors can alter cholinergic and/or dopaminergic activity. This study examined the effects of Delta(8)-tetrahydrocannabinol (Delta(8)-THC) administered acutely (2.5 mg/kg intraperitoneally [ip], 15 min before test) or chronically (5 mg/kg for 30 days followed by 24 h or 7 days of discontinuation) on yawning induced by pilocarpine, a cholinergic agonist (0, 1, 2, 4 or 8 mg/kg ip), or apomorphine, a dopaminergic agonist (0, 20, 40 or 80 mug/kg subcutaneously [sc]). Acute effects of different doses of Delta(9)-tetrahydrocannabinol (Delta(9)-THC: 0, 0.5,.1.25 or 2.5 mg/kg ip) on yawning induced by pilocarpine (2 mg/kg ip) or apomorphine (40 mug/kg sc) were also investigated. Both pilocarpine and apomorphine produced yawning in a dose-related manner. Acute administration of Delta(8)-THC and Delta(9)-THC significantly reduced yawning induced by both pilocarpine and apomorphine. Chronic administration of Delta(8)-THC did not change yawning induced by either agonist 24 h or 7 days after discontinuation of Delta(8)-THC. However, a high frequency of spontaneous yawning was observed 7 days after Delta(8)-THC discontinuation. These results suggest that cannabinoid agonists inhibited yawning induced by cholinergic or dopaminergic agonists. in addition, the increased frequency of spontaneous yawning following cessation of chronic administration of a cannabinoid agonist may be of importance as a withdrawal sign for these drugs. (C) 2002 Elsevier Science Inc. All rights reserved.
Acesso aberto (Open Access)
Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures
(Frontiers Research Foundation, 2013-05-09) Santos Castelhano, Adelisandra Silva; Teada Cassane, Gustavo dos Santos; Scorza, Fulvio Alexandre [UNIFESP]; Cysneiros, Roberta Monterazzo; Presbyterian Mackenzie Univ; Universidade Federal de São Paulo (UNIFESP)
Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. the prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. in preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal Se displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal Se in rodents leads to altered anxiety-related and abnormal social behaviors.
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Aplicação do método de interferência de rna na caracterização do papel do receptor p2x7 na epilepsia do lobo temporal
(Universidade Federal de São Paulo (UNIFESP), 2014-12-30) Amorim, Rebeca Padrao [UNIFESP]; Fernandes, Maria Jose da Silva Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Introduction: Epilepsy is a serious neurological disease, and temporal lobe epilepsy (TLE) is the most common type in adults. Hippocampal sclerosis is the major histopathological alteration in ELT. Hippocampal sclerosis can be reproduced in rats following pilocarpine-induced status epilepticus (SE). Pilocarpine, a cholinergic agonist, when injected in high doses, systemically, induces SE which is followed by neuronal death, synaptic reorganization and hyperexcitability, resulting in spontaneous and recurrent seizures. Cell signaling mediated by P2X7 receptors (P2X7R) has been suggested as an important epileptogenic mechanism. P2X7R activation has been associated with increased intracellular calcium, excitotoxicity, inflammation cascades activation and cell death. Aims: To standardize the RNA interference (RNAi) method to study the in vivo silencing of P2X7R and its role in epileptogenesis using the pilocarpine model. Methods: To standardize small interfering RNA (siRNA) was used a fluorescent oligonucleotide (BLOCK-ITTM), administered by three pathways: intranasal, tail intravenous and intra-hippocampal (ih). The BLOCK-ITTM was complexed to the transfection agent RVG-9dR. The P2X7R knockdown was studied measuring the protein level by western blot. Neuronal death was assayed by Fluoro-Jade B (FJ-B) in brain slices of rat after ih and intracerebroventricular (icv) P2X7R siRNA administration. The hippocampal formation and its subregions volume were studied 48 hours after icv RNAi. Behavioral alterations were performed within 60 days after SE induction in animals subjected to pilocarpine model or saline, that received icv RNAi or vehicle (Groups: Saline-Vehicle, Saline-RNA, Pilo-Vehicle and Pilo-RNA). Results: The ih application of BLOCK ITTM:RVG-9dR complex showed the intracellular fluorescence presence in the hippocampal formation. 48 hours after icv administration of siRNA there was lower P2X7R protein level in the hippocampal formation of Saline-RNA (-43%) and Pilo-RNA (-37%) groups than the respective vehicle groups. The P2X7R knockdown reduced the number of FJ-B-stained cells in the CA1 and CA3 regions, increased latency to the first spontaneous seizure, decreased the number of recurrent spontaneous seizures and normalized the volume of hilus, dentate gyrus suprapyramidal granule cells layer, CA1 and CA3. Conclusions: According to these results, we conclude that RNAi in vivo was effective in the P2X7R knockdown in the hippocampal formation and it protects against injury caused by SE, prevents edema, reduces cell death in the hippocampal formation and minimizes the epileptic seizures manifestations.
Acesso aberto (Open Access)
Avaliação de parâmetros cardíacos em animais com epilepsia: possível causa de morte súbita?
(Academia Brasileira de Neurologia - ABNEURO, 2005-12-01) Colugnati, Diego Basile [UNIFESP]; Gomes, Paulo Alberto Paes; Arida, Ricardo Mario [UNIFESP]; Albuquerque, Marly de [UNIFESP]; Cysneiros, Roberta Monterazzo [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Scorza, Fulvio Alexandre [UNIFESP]; Universidade de Mogi das Cruzes Núcleo de Pesquisas Tecnológicas; Universidade Federal de São Paulo (UNIFESP); UMC NPT Laboratório de Neurociências; Centro Universitário São Camilo; UMC
Among the causes for sudden death in epilepsy, cardiac dysfunction has been an area of interest. Based on this, the aim of our study was to evaluate the heart rate (in vivo and in vitro) and ventricular pressure in vitro of rats with epilepsy induced by pilocarpine. Adult male Wistar rats (n=6) were given pilocarpine hydrochloride to induce status epilepticus. Control rats (n=6) received saline solution instead pilocarpine. Our results showed significant differences in the mean of heart rate in vivo between the groups. In contrast, we did not find differences during in vitro experiments. Our results suggest a central nervous system modulation on the heart, which could explain the sudden unexpected death in epilepsy.
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Avaliação do tratamento com n-acetilcisteína nas manifestações comportamentais e histológicas causadas pela pilocarpina
(Universidade Federal de São Paulo (UNIFESP), 2015-06-30) Patsis, Vassiliki de Brito [UNIFESP]; Fernandes, Maria Jose da Silva Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Epilepsy is the most common neurological dysfunction, affecting more than 65 million people worldwide. Temporal lobe epilepsy (TLE) is the most prevalent form in adults, affecting 40% of all cases. Hippocampal sclerosis is frequently observed in patients with mesial TLE, characterized by cell loss in the hippocampal subregions (CA1, CA3 and hilus), gliosis, granular cell dispersion and mossy fiber sprouting. The increase in intracellular calcium has been associated with lesion resulting from seizures by production of reactive oxygen species, reactive nitrogen species and consequent oxidative stress. The control of oxidative stress by antioxidants may represent a challenge for epileptologists. N-acetylcysteine (NAC) is an antioxidant derivated of the L-cysteine aminoacid usually used in clinic as acetaminophen detoxified. NAC restores glutathione levels, the larger endogenous antioxidant, it modulates glutamatergic, neurotrophic and inflammatory pathways. However, little is known about the effect of NAC in epilepsy. Pilocarpine (Pilo) is a cholinergic agonist that mimics TLE in rats. Objectives: The present study verified the effects of the treatment with NAC considering their antioxidatives properties in the epileptogenic process caused by Pilo. Methods: Wistar rats, males, adults, 2 months old, weighing about 300g, submitted to Pilocarpine (360 mg/kg, intraperitoneal), treated with NAC ad libitum during 8 weeks. NAC was administered by gavage (24mg/day) for 7 days, and ad libitum in the water of the drinking fountains (600 mg/L) in the 7 weeks that followed. The following groups were studied: Saline-Water, Saline-NAC, Pilo-Water and Pilo-NAC. Behavioral analysis was done by video surveillance to check the amount and intensity of seizures during these 7 weeks. The Fluoro-Jade B (FJ-B) was used as marker of neuronal degeneration in the hippocampal subregions. The analysis of free radicals and antioxidants was taken respectively by measuring of NO, MDA, GSH and GSH total. Results: There was a reduction in seizure frequency in Pilo-NAC rats when compared to Pilo-Water. Histological analysis found neurodegeneration in CA1, CA3 and hilus in Pilo group (Pilo-Pilo-Water and NAC) and NAC did not change this pattern of cell loss. There was normalization of the levels of NO and MDA in treatment of NAC compared to Pilo-Water group. There was no statistical differences in the levels of GSH and GSH-total between experimental groups. Conclusions: According to our data, NAC normalized the levels of NO and MDA which were increased by seizures, but was not able to preventing the hippocampal neurodegeneration caused by Pilo. However, because of the improvement in behavior, the NAC can be considered as a possible adjunct therapy in the treatment of epilepsy.
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BASAL DENDRITES ARE PRESENT in NEWLY BORN DENTATE GRANULE CELLS of YOUNG BUT NOT AGED PILOCARPINE-TREATED CHRONIC EPILEPTIC RATS
(Elsevier B.V., 2010-10-27) Avanzi, R. D. T. [UNIFESP]; Cavarsan, C. F. [UNIFESP]; Santos, J. G.; Hamani, C. [UNIFESP]; Mello, L. E. [UNIFESP]; Covolan, Luciene [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fac Ciencias Med Santa Casa de São Paulo
Epilepsy is known to influence hippocampal dentate granule cell (DGC) layer neurogenesis. in young adult rats, status epilepticus (SE) increases the number DGC newly borne cells and basal dendrites (BD), which persist at long-term. in contrast, little is known on whether these phenomena occur in elderly epileptic animals. in the present study, we compare DGC proliferation and the incidence of BD in young and aged pilocarpine-treated rats. Three epileptic groups were considered: Young animals given pilocarpine at 3 months of age. Aged animals treated with pilocarpine at 3 months of age that were sacrificed at 17-20 months. Aged animals that had pilocarpine and developed SE at 20 months, being sacrificed 2 months later. Nine days prior to sacrifice, animals underwent swimming sessions in the Morris water maze as a protocol for the development of hippocampal neurogenesis. We found a higher incidence of newly born DGC cells in young as compared to aged epileptic animals (P<0.001). This later group however, was not homogeneous. While a significant increase in DGC neurogenesis was observed when aged animals with long lasting epilepsy were compared to non-epileptic controls (P<0.01), this has not been recorded in aged animals that had epilepsy for only 2 months (P>0.05). When the number of DGC containing BD was considered, a significantly higher incidence was observed in young as compared to aged epileptic rats (P=0.001). Animals in this later group virtually lacked BD in newly formed dentate gyrus (DG) cells. Based on these results we conclude that plastic changes during epileptogenesis and the development of a pathological substrate in young animals is associated with DGC proliferation and the emergence of BD. As aging occurs, DGC neurogenesis can still be induced in rats with a long-term history of epilepsy but the emergence of BD is markedly reduced. (C) 2010 IBRO. Published by Elsevier B.V. All rights reserved.
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Blockade of pilocarpine- or kainate-induced mossy fiber sprouting by cycloheximide does not prevent subsequent epileptogenesis in rats
(Elsevier B.V., 1997-05-02) Longo, B. M.; Mello, LEAM; Universidade Federal de São Paulo (UNIFESP)
Post-injury sprouting of hippocampal messy fibers has been suggested to be a causal mechanism underlying the development of temporal lobe epilepsy. However, this hypothesis rests entirely on indirect correlational evidence. Here we demonstrate that cycloheximide, a protein synthesis inhibitor, blocked pilocarpine- and kainate-induced messy fiber sprouting in rats, bur did not prevent the subsequent development of spontaneous seizures or affect their frequency. These results provide direct evidence against a causal role for messy fiber sprouting in temporal lobe epileptogenesis. (C) 1997 Elsevier Science Ireland Ltd.
Acesso aberto (Open Access)
Caracterização fisiopatológica do sistema renina-angiotensina durante o status epilepticus induzido pela pilocarpina em camundongos transgênicos que expressam tonina de rato
(Universidade Federal de São Paulo (UNIFESP), 2013-12-20) Iha, Higor Alves [UNIFESP]; Mazzacoratti, Maria da Graca Naffah Mazzacoratti [UNIFESP]; Gouveia, Telma Luciana Furtado Gouveia; http://lattes.cnpq.br/5872912520546019; http://lattes.cnpq.br/3202325307358102; http://lattes.cnpq.br/7202294193275511; Universidade Federal de São Paulo (UNIFESP)
Objectives: To evaluate the influence of pilocarpine induced long-term convulsive seizure in transgenic mice with overexpressed plasma and brain Ang II. Methods: Using a 320mg/kg pilocarpine dose to induce SE. Following the injection protocol of CAVALHEIRO (1995). We conducted an investigation of both strains (TGM (rTon) and WT C57Black/6) of the following groups: a) saline group; b) 3 hour in SE group; and c) Tonic-clonic seizure group. The last group was created upon the greater incidence of such crises in rTon when compared with WT. During the SE, we accessed several parameters such as latency for the first seizure, tonic-clonic seizure susceptibility and mortality. In their hippocampi was assessed by western-blot, real-time RT-PCR, respectively, protein and RNAm expression levels of AT1, AT2, B1 and B2 receptors as well as of the ACE ACE2, iNOS and eNOS enzymes. The same was made to AT1 receptor in heart. It was also assessed the enzymatic activity of hippocampal, cardiac and plasmatic ECA. Results: In an assessment of how both strains reacted to the pilocarpine induced SE we found no difference on first seizure latency time, but a significant higher frequency of death during the generalized tonic-clonic seizure in rTon mice, 66% in rTon and 34% in WT. In RAS, KKS and NO analyzed parameters we found in studied mice groups strain comparison that rTon showed: a) Saline group: in mRNA hippocampal expression, greater transcript level for iNOS and lower for B1 receptor, in protein quantifying, greater for hippocampal AT1 receptor and lower for cardiac AT1 receptor, thereafter, on ECA enzymatic activity evaluation, greater in hippocampi and heart a and on ACE activity, in heart on AT1 receptor protein levels and in plasma on ACE activity; b) in Tonic-Clonic group: mRNA levels were reduced transcripts of eNOS and iNOS, protein quantification showed raised in hippocampi raised ECA2 and lowered B1 receptor and in heart raised AT1 receptor, thereafter, in ECA enzymatic activity assessment, increased in hippocampal and in plasmatic forms. c) 3h of SE group: in hippocampi mRNA levels were upkeeped for ECA transcript, raised for ECA2 and eNOS transcript and reduced for iNOS transcript, protein analysis showed greater raised hippocampal and heart AT1 receptor and hippocampal lowered B2 receptor. Thereafter, on ECA enzymatic activity evaluation, showed raised activity on hippocampal and plasmatic forms. Conclusion: Transgenic mice showed in assessed tissues differences on RAS, KKS and iNOS expression. These differences resulted in a differentiated response to pilocarpine induced seizure in RAS, KKS, iNOS and eNOS which culminated in a greater propensity to tonic-clonic seizures and greater frequency of death throughout the SE, but didn´t affected the latency period for the first seizure.
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Castration in female rats modifies the development of the pilocarpine model of epilepsy
(Elsevier B.V., 2002-05-01) Valente, S. G.; Naffah-Mazzacoratti, M. G.; Pereira, M.; Silva, I; Santos, N. F.; Baracat, E. C.; Cavalheiro, E. A.; Amado, D.; Universidade Federal de São Paulo (UNIFESP)
Previous studies have shown that the susceptibility to pilocarpine-induced status epilepticus (SE) in female rats changes according to estrous cycle phases. These studies have also shown that following pilocarpine administration changes occur in gonadal, hypophyseal and hypothalamic hormones that could contribute for the sequence of the epileptic events. Accordingly, the present work aimed to investigate the role of sexual hormones withdrawal on the development of the pilocarpine model of epilepsy in female rats, With this purpose, castrated and non-castrated adult female Wistar rats were injected with pilocarpine and some characteristic parameters of the experimental model were observed. the results showed increased mortality after pilocarpine injection in the castrated rats when compared with non-castrated females. the latency period for SE onset and for the first spontaneous seizure was decreased in castrated when compared with non-castrated animals. the mossy fiber sprouting measured by neo-Timm scale during the chronic period, reached grade 3 for castrated epileptic rats while the non-castrated epileptic rats showed grade 2. Our results indicate that castration interferes with the epileptogenesis in the pilocarpine model of epilepsy suggesting that female sexual hormones could have protective effects against pilocarpine-induced SE. (C) 2002 Elsevier Science B.V. All rights reserved.
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Cholinergic modulation of inhibitory avoidance impairment induced by paradoxical sleep deprivation
(Elsevier B.V., 2000-05-01) Bueno, OFA; Oliveira, MGM; Lobo, L. L.; Morais, P. R.; Melo, FHM; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
1. Male Wister rats were submitted to paradoxical sleep deprivation for 96 hr by a modified multiple platform technique.2. Training of step-through inhibitory avoidance was performed immediately after the last day of paradoxical sleep deprivation. Twenty-four hr after training the animals were submitted to the retention test.3. in Experiment 1, pilocarpine (4 mg/kg, i.p.) or atropine (4 mg/kg, i.p.) were administered daily during. the paradoxical sleep deprivation period. Pilocarpine, but not atropine, reversed the impairment induced by PS deprivation.4. in Experiment 2, pilocarpine (4, 8 and 12 mg/kg, i.p.) was injected 1 hr before training in order to verify if the reversal of memory impairment was an effect secondary to residual enhanced blood levels of pilocarpine during training. Acute treatment with pilocarpine, in any dose, did not reverse the impairment produced by paradoxical sleep deprivation5. Activation of the cholinergic system during the period ol:deprivation is able to prevent memory deficits induced by paradoxical sleep deprivation.
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Composição celular absoluta do cérebro de animais com epilepsia em diferentes fases da vida adulta
(Universidade Federal de São Paulo (UNIFESP), 2014-06-30) Lopim, Glauber Menezes [UNIFESP]; Arida, Ricardo Mario Arida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Epilepsy is a chronic neurological disorder characterized by permanent brain predisposition to generate epileptic seizures, reaching approximately 50 million people around the world. Temporal lobe epilepsy is the most common form of human epilepsy, being reported extensive loss of pyramidal neurons from hippocampal region, hilar neurons from the dentate gyrus and gliosis. Many features of temporal lobe epilepsy are reproduced in animals by the pilocarpine model. This study investigated the frequency of epileptic seizures in animals throughout adulthood and subsequently quantified the number of cells in different brain regions (cortex, hippocampus, cerebellum and remaining regions) of these animals. Sixty Wistar rats were divided into control and epilepsy groups (9 animals per group). Seizures were video-monitored during 360 days, 24 hours a day. The number of cells was quantified by the technique of isotropic fractionation on the 30th, 180th and 360th day after the first spontaneous seizure. Our results showed a progressive increase in the frequency of spontaneous seizures in the early months, followed by a reduction from the seventh month, and later a stabilization from the tenth to the twelfth month. Statistical analysis (ANOVA for repeated measures) showed higher number of seizures in the fourth and sixth months compared to the first (p=0.001, p=0.006), second (p=0.006, p=0.005) and eleventh (p=0.012, p=0.002) months. The total number of brain cells was lower in rats with epilepsy compared to control animals (p<0.005). Animals with epilepsy had fewer cortical and cerebellar cells at 30, 180 and 360° (p<0.005, p<0.005). In the hippocampal for mation, this reduction occurred in 180° (p<0.001) and 360° days (p=0.01). In the re maining regions, the reduction occurred at 30° and 180° days (p<0.001). A correlat ion between the frequency of recurrent seizures and the number of cells in the hippocampal formation was noted. Animals presenting more seizures showed less cell number at the 30° (r=-0.828, p=0.006) and 360° days (r=-0.729 , p = 0.017). Our findings demonstrate that there is an relation between frequency of spontaneous seizures and number of brain cells throughout the life of animals with epilepsy, and this depends on investigated area and age of animals.
Acesso aberto (Open Access)
The contribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy
(Academia Brasileira de Neurologia - ABNEURO, 2002-09-01) Scorza, Fulvio Alexandre [UNIFESP]; Arida, Ricardo Mario [UNIFESP]; Priel, Margareth [UNIFESP]; Calderazzo, Lineu [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Universidade de Mogi das Cruzes; Universidade Federal de São Paulo (UNIFESP)
The pilocarpine model of epilepsy in rats is characterised by the occurrence of spontaneous seizures (SRSs) during the chronic period that recur 2-3 times per week during the whole animal life. In a previous study on brain metabolism during the chronic period of the pilocarpine model it was possible to observe that, among several brain structures, the lateral posterior thalamic nuclei (LP) showed a strikingly increased metabolism. Some evidences suggest that the LP can participate in an inhibitory control system involved in the propagation of the seizures. The aim of the present study was to verify the role of LP in the expression and frequency of spontaneous seizures observed in the pilocarpine model. Ten adult male rats presenting SRSs were monitored for behavioural events by video system one month before and one month after LP ibotenic acid lesion. Another group of chronic epileptic rats (n=10) had the anteroventral thalamic nuclei (AV) lesioned by ibotenic acid. After the surgical procedure, the animals were sacrified and the brains were processed for histological analysis by the Nissl method. The LP group seizure frequency was 3.1±1.9 before ibotenic acid injection and showed an increase (16.3±7.2 per week) after LP lesion. No changes in SRSs frequency were observed in the AV group after ibotenic lesion in these nuclei. These results seem to suggest that LP play a role in the seizure circuitry inhibiting the expression of spontaneous seizures in the pilocarpine model.
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The course of untreated seizures in the pilocarpine model of epilepsy
(Elsevier B.V., 1999-04-01) Arida, R. M.; Scorza, F. A.; Peres, CDA; Cavalheiro, E. A.; Universidade Federal de São Paulo (UNIFESP)
The course of untreated epilepsy is not well. established. This study uses a model of chronic limbic epilepsy (pilocarpine model of epilepsy) to determine the pattern of occurrence of seizures in untreated animals. Following pilocarpine administration, 21 rats were monitored continuously with a video system for 135 days after the first spontaneous seizure. Animals showed a great variability in seizure numbers and were divided in two subgroups presenting either a low frequency of seizures (n = 9 animals presenting ten or less seizures in the first 15 days of observation) or a high frequency of seizures (n = 12 animals presenting more than ten seizures during this period). Animals with low number of seizures during the first 15 days of observation showed a significant increase in seizure frequency in the following period of analysis (until 105 days). On the other hand, those with initial high number of seizures showed Significant changes in seizure frequency only in the first 2 months. the duration of each spontaneous seizure did not change significantly over time. These findings show that in untreated epilepsy there is a maturation process in the early stages and this accelerating process can be of predictive value for the treatment of epilepsy. (C) 1999 Elsevier Science B.V. All rights reserved.
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Damage, reorganization, and abnormal neocortical hyperexcitability in the pilocarpine model of temporal lobe epilepsy
(Blackwell Publishing Inc, 2002-01-01) Sanabria, Emilio Rafael Garrido [UNIFESP]; Silva, Alexandre Valotta da [UNIFESP]; Spreafico, R.; Cavalheiro, Esper Abrão [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ist Nazl Neurol C Besta
Purpose: Clinical, neuropathological, and electro-physiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). in most cases, limbic-originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. the present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine-treated epileptic rats.Methods: Adult epileptic animals showing six to seven seizures/week and saline-injected rats were selected for neurohistology. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and stained with cresyl violet (Nissl). Immunocytochemistry (ICC) was performed using anti-neurofilament (SMI-311) antibody. Extracellular (layer II/III) and intracellular (layer V) recordings were per-formed in coronal sensorimotor neocortical slices. Several electrophysiological aspects were examined such as evoked responses, intrinsic properties, and firing patterns of layer V pyramidal cells.Results: Niss1 staining showed a significant decrease of cortical thickness in epileptic rats when compared with controls, particularly in superficial layers (II-IV). Such abnormalities were also revealed by SMI-311 staining. SMI-311-labeled dendrite arborizations were more complex in layers I-II of epileptic rats. Epileptic rats manifested several abnormalities in extracellular field responses including hyperresponsiveness and presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-mediated polysynaptic activity. Although no significant changes were observed concerning passive intrinsic properties, it was possible to detect a higher proportion of bursting neurons distributed in layer V (60%) of epileptic rats compared with 22% in control slices.Conclusions: Taken together, our findings indicate damage, reorganization, and chronic hyperexcitability of sensorimotor neocortex in experimental TLE.
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Deep brain stimulation of the anterior nucleus of the thalamus: Effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus
(Elsevier B.V., 2008-02-01) Hamani, Clement; Hodaie, Mojgan; Chiang, Jason; del Campo, Martin; Andrade, Danielle M.; Sherman, David; Mirski, Marek; Mello, Luiz E. [UNIFESP]; Lozano, Andres M.; Univ Toronto; Toronto Western Hosp; Johns Hopkins Univ; Universidade Federal de São Paulo (UNIFESP)
Purpose: Electrical stimulation of the anterior nucleus of the thalamus appears to be effective against seizures in animals and humans. As the optimal stimulation settings remain elusive, we studied the effects of different stimulation parameters against pilocarpine induced seizures and status epilepticus (SE).Methods: Adult rats had electrodes implanted bilaterally into the AN. Five days later, different groups of animals were stimulated with 1000 LA, 500 LA, or 200 mu A and frequencies of either 20 Hz or 130 Hz. Pilocarpine (350 mg/kg i.p.) was injected 5 min after stimulation onset and seizures were monitored. Sham-treated controls had electrodes implanted but did not receive stimulation until they developed SE. After SE, these animals had the electrodes turned on to assess whether AN stimulation could arrest ongoing ictal activity.Results: Compared to sham-treated controls (n = 8), stimulation at 500 mu A (n = 13) significantly increased the latency for seizures and SE by 1.9-2.2-fotd. in contrast, stimulation at 1000 mu A (n=8) produced a non-significant decrease in the latencies to these events. No major effect was observed with stimulation at 200 mu A (n = 11). Similar results were obtained for each current intensity, regardless of the stimulation frequency used (20 Hz and 130 Hz). in sham-treated controls that had the electrodes turned on after SE, stimulation was not able to arrest ongoing ictal activity.Conclusions: the anticonvulsant effects of AN stimulation against pilocarpine-induced seizures were mainly determined by the current and not the frequency of stimulation. AN stimulation initiated after SE onset was ineffective. (C) 2007 Published by Elsevier B.V.
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Disruption of light-induced c-Fos immunoreactivity in the suprachiasmatic nuclei of chronic epileptic rats
(Elsevier B.V., 1996-09-27) Sanabria, ERG; Scorza, F. A.; Bortolotto, Z. A.; Calderazzo, L. S.; Cavalheiro, E. A.; Universidade Federal de São Paulo (UNIFESP)
Photic stimulation during specific day periods may induce Fos oncoprotein expression within the ventrolateral part of the suprachiasmatic nucleus (SCN) in the hypothalamus of rodents. This phenomenon appears to be a major molecular mechanism for environmental light/dark cycle entrainment of the mammalian circadian clock. Light-dependent synchronization of circadian rhythmicity may be disrupted in epilepsy, a chronic neurological disorder often associated with chronobiological features such as seizure periodicity and disruption of endogenous biological rhythms. the present work examined the light-induced Fos protein expression on the SCN in the pilocarpine model of chronic epilepsy. Fos-like immunoreactivity was significantly reduced in the SCN of chronic epileptic rats after photic stimulation during the subjective night. These results indicate an altered Fos protein expression in the SCN of chronic epileptic rats. the present findings reveal that pathological neural events underlying epileptogenesis may disturb circadian rhythm regulation. the experimental study of circadian clock activity in the SCN may clarify the molecular bases of chronobiological disturbances in epilepsy.
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Distribuição e expressão dos receptores de melatonina no hipocampo de ratos submetidos ao modelo de epilepsia induzida por pilocarpina
(Universidade Federal de São Paulo (UNIFESP), 2014-10-31) Rocha, Anna Karynna Alves de Alencar [UNIFESP]; Scerni, Debora Amado Scerni [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Studies from our laboratory have shown a neuroprotective effect of melatonin on pilocarpine-induced epilepsy. The pinealectomy is able to facilitate the epileptogenesis while the melatonin exerted a neuroprotection in the epilepsy model induced by pilocarpine, indicating a major role of melatonin in this condition. However, no consistent data are published about the dynamic changes of melatonergic system in the natural course of temporal lobe epilepsy. Dysfunctions in the melatonin signaling pathway may be primarily based on changes in the density of their receptors. Moreover, altered receptor expression may be a consequence of neurodegenerative processes. Therefore, our study aimed to verify if status epilepticus-induced by pilocarpine cause alterations in the distribution and gene expression of melatonin receptors, MT1, MT2 and ROR? in rat hippocampus. For this, we compared the differences in mRNA expression of MT1, MT2 and ROR? receptors in acute, silent and chronic phases of the model compared to controls within a period of 24 hours by RT-PCR in real time as well as the difference in the location and intensity of immunostaining of these receptors in the same phase by immunohistochemistry.Therefore, our study found that the pilocarpine-induced status epilepticus caused short and long-term changes in the distribution and gene expression of melatonin receptors, MT1, MT2 and ROR? in rat hippocampus. There is an increase in the expression of MT1 and MT2 receptor in the initial hours of the status epilepticus. During the following phases of the model (silent and chronic) there is a reduction in the expression of these receptors in various hippocampal subregions. In contrast to membrane receptors, the expression of nuclear receptor ROR? presented a drastically reduction during the acute phase and the silent phase. In the chronic phase, the presence of these nuclear receptors returns to levels similar of controls. Therefore, we can suggest that the increase in the expression of MT1 and MT2 receptors may be a compensatory mechanism due to the loss of receptors during injury, as the attempt to ?capture? more melatonin. Also, we hypothesized that these receptors might be involved in mechanisms of neuroprotection. Moreover, taking into account the beneficial effect of melatonin via ROR? by modulating of the inflammation and excitotoxicity, we suggest that the reduction of these receptors in the early stages of the pilocarpine model of epilepsy may negatively influence the development of epilepsy, facilitating the epileptogenesis. The correct mechanism related to the decrease and later increase in the expression of this receptors are unknown and needs further investigations.
Acesso aberto (Open Access)
Effect of aerobic physical exercise in pinealectomized animals submitted to the pilocarpine model of epilepsy
(Liga Brasileira de Epilepsia (LBE), 2006-06-01) Siliano, Marcelo Reina [UNIFESP]; Lima, Eliângela de [UNIFESP]; Valente, Sandra Gomes [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Arida, Ricardo Mario [UNIFESP]; Amado, Débora [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de Mogi das Cruzes Núcleo de Pesquisas Tecnológicas Laboratório de Neurociências
OBJECTIVE: To better clarify the positive effects of physical exercise in the epilepsy, we analyzed the effect of the pinealectomy in animals with temporal lobe epilepsy (TLE) induced by pilocarpine submitted to an aerobic physical program. MATERIAL AND METHODS: Forty adults Wistar rats were used: 1) PX + CHRONIC - Pinealectomized animals (PX) with TLE (CHRONIC) without exercise (n = 9); 2) PX + CHRONIC + EXERCISE - submitted to an aerobic physical exercise program (n = 5); 3) CHRONIC - without exercise (n = 8); 4) CHRONIC + EXERCISE (n = 8); 5) CTRL - control without exercise (n = 5); 6) CTRL + EXERCISE (n = 5). The physical exercise program consisted of 1 hour of treadmill, 5 days/week, during 30 days, at 60% VO2max. The Nissl and neo-Timm methods were used. RESULTS: The pinealectomy increased the frequency of seizures in animals with epilepsy. It was observed a reduction of the neuronal death and mossy fiber sprouting in the animals with epilepsy submitted to an aerobic physical exercise program. However, the physical exercise program did not modify the frequency of the seizures in the pinealectomized animals.
Acesso aberto (Open Access)
Effect of glycemic state in rats submitted to status epilepticus during development
(Academia Brasileira de Neurologia - ABNEURO, 2006-06-01) Santiago, Joselita Ferreira Carvalho [UNIFESP]; Carvalho, Fatima Ferreira [UNIFESP]; Perosa, Sandra Regina [UNIFESP]; Siliano, Marcelo Reina [UNIFESP]; Cruz, José Walber Miranda Costa; Fernandes, Maria Jose da Silva [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Amado, Débora [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Instituto do Coração
The effect of glycemic state on status epilepticus (SE) development was studied in animals of different ages, submitted to pilocarpine model of epilepsy. Groups: I- Rats with 9-day-old (P9): IA. Submitted to 1SE; IB. Saline-treated; IC. Induced- hyperglycemia; ID. Induced- hyperglycemia+SE; II- Rats submitted to three consecutive episodes of SE at P7, P8 and P9; III- Rats submitted to 1SE at P17; IV- Rats submitted to 1SE at P21. Hippocampal cell death and the expression of glucose transporter GLUT3 were analyzed in group I. The results demonstrated normoglycemia in the groups IA, IB and II, hypoglycemia in group III and hyperglycemia in group IV, showing that the glycemia during SE is age dependent. Induced hyperglycemia during SE in P9 protected the hippocampal neurons from death and both groups IC and ID presented increased GLUT3 expression, showing high glucose consumption by the hippocampus.
Somente Metadadados
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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