Navegando por Assunto "Epilepsia"

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Ativação microglial, perda neuronal e astrocitose em um modelo experimental de epilepsia do lobo temporal
(Universidade Federal do Pará, 2011-05-12) FERREIRA, Elane de Nazaré Magno; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Epilepsy is one of the most prevalent serious chronic neurological conditions worldwide. The World Health Organization (WHO) estimates 45-50 cases in 100,000 habitants in developed countries, rising to 122 to 190, in developing countries, including Brazil. There are no risk factors in relation to gender, race or age, but it is believed that some gene mutations are associated with an increased risk to develop the disease. The pathophysiology of epilepsy involves complex factors such as loss inhibition and increased neuronal excitability in different brain regions, but mainly at the hippocampus. Mutations in ion channels and in both receptor and neurotransmitter transporters may underlie disease pathogenesis. The inflammatory response plays an important role on epilepsy pathophysiology. Recent experimental evidence suggests a major role for both microglia and astrocyte activation on the seizure exacerbation. In this dissertation, we describe the general patterns of microgial and astrocyte activation and neuronal loss in CA1, CA3, hippocampal hylus, peririnal, lateral entorrinal and motor cortices and amigdaloid complex in the first week following “Status Epilepticus” induced by pilocarpine injection. Immunohistochemistry was performed to label neurons (anti-NeuN), microglia in general (anti-Iba1), activated microglia/macrophages (anti-ED1) and astrocytes (anti-GFAP). Numbers of neurons and activated microglia were counted in the hippocampus. There was intense microglia and astrocyte activation in all motor and limbic regions studied, mainly at 3 and 7 days post SE. Minocycline treatment reduced microglia activation in the hippocampus (p<0.05), without affecting astrocytosis. There was considerable inflammation in regions outside the hippocampus with an early inflammatory response. There was no neuronal loss in the hippocampus in the first week following SE, although sporadic alterations on neuronal morphology have been observed. These results suggest that the inflammatory response is an early and generalized histopathological event in several motor and limbic structures following pilocarpine-induced SE, even in the absence of conspicuous cell loss. The patterns of microglia and astrocyte activation can be used as markers of the progressive tissue impairment in the experimental models of epilepsy.
Acesso aberto (Open Access)
Avaliação anticonvulsivante e pró-convulsivante de óleos essenciais de Lippia origanoides e Rosmarinus officinalis em ratos: um estudoeletrofisiológico
(Universidade Federal do Pará, 2025-05) ARAÚJO, Daniella Bastos de; HAMOY, Moisés; http://lattes.cnpq.br/4523340329253911; https://orcid.org/0000-0002-2931-4324
Epilepsy is a neuronal disorder characterized by abnormal brain excitability, leading to seizures. Only about 66% of epileptic patients respond adequately to treatment with existing conventional anticonvulsants, making it necessary to investigate new antiepileptic drugs. The growing research on natural products and their pharmacological properties has become increasingly promising, particularly in the study of essential oils, already widely used in popular culture for the treatment of several diseases. The present studies evaluated the anti- and pro-convulsant effects of the essential oils of Lippia origanoides (LOEO) and Rosmarinus officinalis (EORO) in Wistar rats. We evaluated the essential oil of Lippia origanoides (LOEO) (100 mg/kg i. p.) in comparison with diazepam (DZP) (5 mg/kg i. p.) and the combined administration of these two substances to control seizures induced by pentylenetetrazole (PTZ) (60 mg/kg i. p.). This evaluation was carried out using 108 male Wistar rats, which were divided into two experiments. Experiment 1 – Behavioral evaluation and Experiment 2 – Electrocorticographic evaluation. With rosemary essential oil, we evaluated high doses in 54 Wistar rats, weighing between 180 and 200 g. The study consisted of three experiments: 1) behavioral monitoring of the animals after administration of 500 mg/kg i.p.; 2) electrocorticographic recordings after drug administration; 3) reaction to anticonvulsant drugs, where phenytoin, phenobarbital and diazepam (10 mg/kg i.p.) were administered. With LOEO, the animals presented a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the groups treated with LOEO. Combined treatment with diazepam resulted in increased anticonvulsant effects, while with EORO, the results demonstrated an increase in the latency time for the onset of isolated clonic seizures without loss of the postural reflex. The animals showed a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the groups treated with LOEO. Combined treatment with diazepam resulted in increased anticonvulsant effects. Treatment with LOEO was effective in controlling seizures, and its combination with diazepam may represent a future option for the treatment of difficult-to-control seizures, while treatment with EORO demonstrated an excitatory activity related to the reduction of GABAergic activity.
Acesso aberto (Open Access)
Avaliação pré-clínica da duloxetina em modelo de convulsão: análise comportamental, eletroencefalográfica e influência no estresse oxidativo
(Universidade Federal do Pará, 2014-06-17) COELHO, Danielle Santana; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Epilepsy is a disorder with high prevalence and severity. Although there are several anticonvulsant drugs available in the market, 30 to 40% of the patients are refractory to the treatment. Besides the seriousness of epilepsy per se, this disorder may be accompanied by many comorbidities such as depression, which is the main psychiatric comorbidity of epilepsy. The mechanisms involved in the relationship between epilepsy and depression are not clarified. Given that some anticonvulsant drugs can trigger or enhance depressive symptoms, while some antidepressant drugs can potentiate the severity of seizure, the concomitant treatments of both disorders can be problematic. On the other hand, some studies have shown that antidepressant drugs can be safe and even possess an anticonvulsant activity such as venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI). Considering that duloxetine, another SNRI, has a more potent inhibition of monoaminergic transporters and that there is no study about its influence on seizures, the aim of our study is to verify the potential anticonvulsant action of duloxetine against seizures induced by pentylenetetrazole (PTZ) on mice. With this aim, mice will be pre-treated with duloxetine (10, 20, 40 mg/kg/i.p.), and thirty minutes after, the animals will receive an intraperitoneal injection of PTZ (60 mg/kg, i.p.). In the following twenty minutes the animals are going to be evaluated. The threshold for the first myoclonic jerk, tonic-clonic seizure, the duration of seizures and survival will be quantified. The electroencephalographic analysis (EEG) was used to assess the severity of the seizures (wave’s amplitude increase). After this period the animals will be sacrificed, the cerebral cortex dissected and biochemical analysis (activity of superoxide dismutase (SOD), catalase (CAT), nitrite levels and lipid peroxidation) will be made to investigate the mechanisms by which this drug can influence seizures. The results exhibit the anticonvulsant action of duloxetine. The drug was capable of enhancing the threshold for the first myoclonic and tonic-clonic seizures induced by PTZ. Additionally, the EEG demonstrated that duloxetine at the dose of 20 mg/kg decreased significantly the amplitude of the waves while at the dose of 40 mg/kg it increased the amplitude when compared to all the treatments. Regarding the evaluation of duloxetine’s influence on oxidative stress, all the animals treated solely with PTZ presented a significant increase on lipid peroxidation and a decrease on SOD and CAT activity. Concerning nitrites’ level, there was no difference between the treatments. The dose of 20 mg/kg of duloxetine showed a significant protection against the alterations in oxidative stress induced by PTZ. The anticonvulsant action of duloxetine (20 mg/kg) collaborates with the theory which has been presented in the last few years where it is proposed that the modulation of the serotonergic and noradrenergic neurotransmission may exert an anticonvulsant activity. Moreover, the efficiency of duloxetine in preventing the aggravation of oxidative stress involved in the seizures induced by PTZ corroborates with studies that demonstrate that anticonvulsant substances can influence seizures through its antioxidant activity. Given these points, we conclude that duloxetine is a promising adjuvant for the treatment of patients with the comorbidity epilepsy and depression.
Acesso aberto (Open Access)
Caracterização comportamental e eletroencefalográfica das convulsões induzidas pelo cunaniol e acetato de cunaniol extraídos das folhas de Clibadium sylvestre, um modelo de convulsão generalizada experimental em ratos (Wistar)
(Universidade Federal do Pará, 2011-12-15) HAMOY, Moisés; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
The Clibadium sylvestre is largely distribued in the Amazon region, where is know as cunambi or cunhambi, and its ingestion causes inebriation or even fish´s death, demonstrating ichthyotoxic property. The compounds existing in the leaf of Clibadium sylvestre are powerful of central nervous system stimulants, its leafs contain potential convulsivant substances. The electroencephalographic changes, seizure and drug effects on seizure behavior control were studied as well as metabolic pathway of compounds cunaniol acetate and cunaniol. The work was performed with adult male Wistar rats, treated with DE50 of 2,92 mg/kg or DL50 of 3,64 mg/kg of cunaniol, administration route used was intraperitoneal. After cunaniol administration, the seizure evolution was observed, it allows to classify them according to the presentation intensity relate to cunaniol plasma concentration. The eletroencefalografic parameters of the drugs action on the seizure control and the clinic characteristic were determined and evaluated. The plasma analysis obtained by liquid chromatography after the application of convulsivant substances indicates that the cunaniol acetate undergoes deacetylation giving rise to cunaniol, drug responsible for convulsive state. Data electrocorticography has been shown five different patterns of tracks during recording with 4 hours remaining changes outlined by 12 hours after application. Among the drugs used to prevent the onset of seizures, the most effective were diazepam, phenobarbital and ketamine. The convulsive behavior was classified into five stages. For the occurrence of stages 4 and 5 there was no statistical differences regarding plasma cunaniol.
Acesso aberto (Open Access)
Classificação de eletroencefalogramas epiléticos em estado de repouso com aplicação de classificadores lineares e um atributo derivado da densidade espectral de potência
(Universidade Federal do Pará, 2019-12-04) FIEL, José de Santana; PEREIRA JÚNIOR, Antonio; http://lattes.cnpq.br/3239362677711162
Millions of Brazilians are affected with epilepsy and the access to early diagnosis is crucial for their adequate treatment. However, epilepsy diagnosis depends on the evaluation of longduration electroencephalographic (EEG) recordings performed by trained professionals, turning it in a time-consuming process which is not readily available for many patients. Thus, the present work proposes a methodology for automatic EEG classification of epileptic subjects which uses short-duration EEG recordings obtained with the patient at rest. The system is based on machine learning algorithms that use an attribute extracted from the power spectral density of EEG signals. This attribute is an estimate of functional connectivity between EEG channel pairs and is called debiased weighted phase-lag index. The classification algorithms were linear discriminant analysis (LDA) and support vector machines (SVM). EEG signs were acquired during the interictal state, i.e., between seizures and had no epileptiform activity. Recordings of 11 epileptic patients and 7 healthy subjects were used to evaluate the method’s performance. Both algorithms reached their maximum classification performances, 100 % accuracy and area under the receiver operating characteristic (AUROC) curve, when a feature vector with 190 attributes was used as input. The results show the efficacy of the proposed system, given its high classification performance.
Acesso aberto (Open Access)
Investigação do potencial cortical provocado visual para padrão reverso em pacientes diagnosticados com epilepsia parcial e generalizada
(Universidade Federal do Pará, 2011-12-02) DUARTE, Regina Célia Beltrão; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718; SILVEIRA, Luiz Carlos de Lima; http://lattes.cnpq.br/9383834641490219
The present work evaluated the visual evoked cortical potential of children with clinical history of epilepsy in order to identify electrophysiological marker indicating cortical changes in epilepsy. Thirty-four subjects with history of epilepsy along the lifetime (18 subjects diagnosed with partial epilepsy and 16 subjects diagnosed with generalized epilepsy). The control group was composed by 19 subjects age-matched with no history of epilepsy. Visual evoked cortical potential components for pattern-reversal presentation of chessboards were evaluated in amplitude, implicit time, and amplitude ratio of components. It was observed that generalized epilepsy patients had larger N75 than other two groups, whilst N75/P100 and P100/N135 ration were smaller in partial epilepsy patients than other groups. There was weak correlation between the electrophysiological parameters and the age of seizures onset or time of antiepileptic drugs intake. In conclusion, N75 amplitude and amplitude ratio can be good electrophysiological markers to cortical changes in epilepsy.
Acesso aberto (Open Access)
Relação entre neurogênese hipocampal e história clínica de pacientes adultos portadores de epilepsia refratária do lobo temporal.
(Universidade Federal do Pará, 2018-09-13) GAMA, Jessica Silva; SOUSA, Regina Célia Gomes de; http://lattes.cnpq.br/5576436464955236; LIMA, Silene Maria Araújo de; http://lattes.cnpq.br/8961057812067156
Epilepsy is a neurological disorder characterized by the permanent predisposition of the brain to generate epileptic seizures, which affects about 1% of the world population. In Brazil, the disease can reach 2% to 4% of the population. Most patients have a good prognosis for drug treatment, however 30% of patients are refractory to treatment. Among the epilepsies that do not present a good prognosis is the Temporal Lobe Epilepsy (ELT). ELT is characterized morphologically by a selective loss of hippocampal neurons, concomitantly with increased hippocampal neurogenesis. It is believed that this exacerbated neurogenesis contributes to epileptogenesis (onset of epilepsy); however, the role of this increased neurogenesis in patients with TLE remains unknown. We used hippocampus from patients with epilepsy, who underwent a surgical procedure in which unilateral hippocampal resection was performed. From the analysis of the same, a possible relationship between neurogenic patterns and the evolution of the disease was investigated. Interviews with patients who underwent surgery demonstrated that the triggering event (precipitant) of epilepsy occurred in the first years of life of the patients. In addition, they were high intensity events, and also presented a high frequency of epileptic seizures and drug refractoriness. Immunohistochemical analysis of hippocampi showed equivalently that there was a perceptible dispersion of the granule cell layer, indicating a possible ectopic migration in labeling for neuroblasts (immature neurons), which are generated in neurogenesis. The results obtained in this work are pioneer, given that they are based on both clinical and histopathological findings, and the relationship between hippocampal neurogenesis and clinical history proposes a new research vision. These findings may also help in a new perspective of differential treatment in temporal lobe epilepsies.