RESUMO
Neuroinflammation plays a protective role in the brain; however, in neurological diseases such as epilepsy, overactivated neuroinflammation, along with overexpression of inflammatory mediators, can cause neuronal tissue damage, which can trigger seizures due to loss of ionic or neurotransmitter homeostasis. Therefore, we aimed to evaluate mRNA expression levels of proinflammatory cytokines, early growth response factor 3 (Egr3), and GABA A receptors in the hippocampus of naive audiogenic mutant tremor mice, and stimulated tremor mice after a seizure. Gene expression of Il-1ß, Il-6, Tnf-α, Ccl2, Ccl3, Egr3, Gabra1, and Gabra4 from hippocampal samples of naive and stimulated tremor mice were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Relative to resistant mice, Ccl3 gene expression was increased and Il6 was decreased in the hippocampus of naïve tremor mice. Thirty minutes after a seizure, Ccl3 and Il-1ß mRNA expression were decreased (p < 0.0001; p = 0.0034, respectively) while Il6 was increased (p = 0.0052) in stimulated tremor mice, relative to naïve animals. In addition, Egr3, Gabra1, and Gabra4 mRNA expression was decreased in the hippocampus of naive tremor mice, relative to resistant mice, which increased 30 minutes after a seizure (p = 0.0496; p = 0.0447, and p = 0.0011, respectively), relative to naïve animals. In conclusion, overexpression of Ccl3 in the hippocampus of naive tremor mice, followed by downregulation soon after seizure in stimulated tremor mice, could be involved in changes in the blood-brain barrier (BBB) permeability in epilepsy. Il-1ß may be involved in hippocampal downregulation of GABA A receptors of naive tremor mice, characterizing an important mechanism in audiogenic seizures triggering. Hippocampal alterations of proinflammatory cytokines, Egr3, and GABA A receptors in tremor mice reinforce them as an alternative tool to modeling temporal lobe epilepsy.
Assuntos
Epilepsia Reflexa , Receptores de GABA-A , Camundongos , Animais , Receptores de GABA-A/metabolismo , Tremor/metabolismo , Convulsões/genética , Hipocampo/metabolismo , Epilepsia Reflexa/genética , RNA Mensageiro , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismoRESUMO
Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy.
Assuntos
Epilepsia Reflexa , Terapia a Laser , Descolamento Retiniano , Feminino , Humanos , Epilepsia Reflexa/cirurgia , Convulsões/etiologia , Convulsões/diagnóstico , Convulsões/cirurgia , Descolamento Retiniano/cirurgia , LasersRESUMO
The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.
Assuntos
Epilepsia Reflexa , Hipotálamo/metabolismo , Excitação Neurológica/fisiologia , Sistemas Neurossecretores/metabolismo , Neuro-Hipófise/metabolismo , Estimulação Acústica , Animais , Modelos Animais de Doenças , Epilepsia Reflexa/genética , Epilepsia Reflexa/metabolismo , Epilepsia Reflexa/patologia , Epilepsia Reflexa/fisiopatologia , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Hipotálamo/patologia , Hipotálamo/fisiopatologia , Excitação Neurológica/patologia , Masculino , Sistemas Neurossecretores/patologia , Sistemas Neurossecretores/fisiopatologia , Ocitocina/sangue , Ocitocina/genética , Ocitocina/metabolismo , Neuro-Hipófise/patologia , Neuro-Hipófise/fisiopatologia , Ratos , Ratos Wistar , Convulsões/genética , Convulsões/metabolismo , Convulsões/fisiopatologia , Convulsões/psicologia , Vasopressinas/sangue , Vasopressinas/genética , Vasopressinas/metabolismoRESUMO
We report a patient with reflex tooth-brushing-triggered epilepsy, associated with a post-central lesion within the right somatosensory face area. Contralateral facial sensory and motor phenomena, associated with contralateral upper limb extension, were present at seizure onset after gingival stimulation, but seizures could also be induced by contact with solid food or liquids. Spontaneous seizures also were recorded. Secondary generalization was infrequent. Stereoelectroencephalography implantation was performed, with seizure recording and cortical/subcortical stimulation for mapping, to identify the precise extent of surgical resection. Complete postoperative control of epilepsy was achieved, accompanied by a mild and transient neurological deficit. [Published with video sequence].
Assuntos
Epilepsia Reflexa/diagnóstico , Epilepsia Reflexa/cirurgia , Córtex Somatossensorial , Adulto , Eletrocorticografia , Feminino , Gengiva/fisiopatologia , Humanos , Córtex Somatossensorial/patologia , Córtex Somatossensorial/fisiopatologia , Córtex Somatossensorial/cirurgia , Técnicas EstereotáxicasRESUMO
The objective of the present study was to evaluate maternal reproductive performance, body weight, and frequency of external and internal anomalies of newborns of Wistar Audiogenic Rat (WAR) females as compared with Wistar rats. The adult WAR and Wistar rats were mated within their respective strains. After confirming the pregnancy, the body weights were weekly evaluated. On day 21 of pregnancy, the female rats were anesthetized and sacrificed to evaluate the maternal reproductive outcomes and biochemical profile, newborn weight, and external and internal anomalies. The WAR strain gained less weight during the pregnancy and presented hyperproteinemia, hypertriglyceridemia, and embryonic losses concerning Wistar rats, suggesting an inadequate intrauterine condition for embryonic development and fetal viability. WAR also presented a higher percentage of newborns classified as small for gestational age related to intrauterine growth restriction, which was confirmed by the lower number of ossification centers. There was a higher percentage of skeletal anomalies compared with fetuses of the Wistar dams, confirming their greater susceptibility during the formation and development of their skeletal system. Thus, the WAR presents physiological alterations compromising the viability of their embryos and fetuses, leading to impaired development of the newborns.
Assuntos
Epilepsia Reflexa/complicações , Epilepsia Reflexa/fisiopatologia , Desenvolvimento Fetal , Complicações na Gravidez/etiologia , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Animais , Peso Corporal , Epilepsia Reflexa/sangue , Feminino , Feto/patologia , Gravidez , Complicações na Gravidez/sangue , Ratos WistarRESUMO
Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexponential trend in Wistar rats, suggestive of a homogeneous population of synapses, but a biexponential trend in WARs. Based on this, we hypothesize that there are two populations of GABAergic synaptic release sites in CA1 pyramidal neurons from WARs. To address this hypothesis, we used a well-established neuronal computational model of a CA1 pyramidal neuron previously developed to replicate physiological properties of these cells. Our simulations replicated the biexponential trend only when we decreased the release frequency of synaptic currents by a factor of six in at least 40% of distal synapses. Our results suggest that almost half of the GABAergic synapses of WARs have a drastically reduced spontaneous release frequency. The computational model was able to reproduce the temporal dynamics of GABAergic inhibition that could underlie susceptibility to the spread of seizures.
Assuntos
Região CA1 Hipocampal/fisiopatologia , Epilepsia Reflexa/fisiopatologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Células Piramidais/fisiologia , Sinapses/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Modelos Animais de Doenças , Ratos , Ratos WistarRESUMO
La epilepsia refleja por agua caliente es un tipo de convulsión poco frecuente cuya fisiopatología se desconoce. Estas crisis reflejas suelen iniciarse pocos segundos tras el contacto con el agua y, comúnmente, a temperaturas de 37-48 ºC. Los automatismos y las crisis parciales complejas, con o sin generalización secundaria, son el modo de manifestación principal.La exploración neurológica y el electroencefalograma intercrítico no suelen presentar alteraciones, lo que puede condicionar un retraso en el diagnóstico, por lo que es fundamental la sospecha clínica.El tratamiento antiepiléptico se inicia cuando se asocia a otro tipo de epilepsia o cuando ciertas medidas sencillas, como el descenso de la temperatura del agua en el baño, no controlan las crisis. Es posible la desaparición espontánea. Cuando es necesaria la terapéutica farmacológica, existe, normalmente, buena respuesta.Se presenta el caso de un lactante con diagnóstico de epilepsia refleja por agua caliente.
Hot-water epilepsy is a rare type of seizure whose pathophysiology is unknown. These reflex seizures usually begin a few seconds after contact with water, commonly at temperatures between 37-48 ºC. Automations and complex partial crises, with or without secondary generalization, are the main manifestation mode of this type of reflex epilepsies.Neurological examination and intercritical electroencephalography are usually normal, which may condition a delay in diagnosis, and the clinical suspicion is fundamental.Antiepileptic treatment is initiated when associated with another type of epilepsy or when certain simple measures, such as lowering the water temperature in the bath, do not control crises. Spontaneous disappearance is possible; when pharmacological therapy is necessary, there is usually a good response.We present the case of an infant diagnosed with hot-water epilepsy.
Assuntos
Humanos , Masculino , Lactente , Epilepsia Reflexa/diagnóstico , Convulsões , Banhos , Epilepsia Reflexa/tratamento farmacológico , Temperatura AltaRESUMO
Hot-water epilepsy is a rare type of seizure whose pathophysiology is unknown. These reflex seizures usually begin a few seconds after contact with water, commonly at temperatures between 37-48 ºC. Automations and complex partial crises, with or without secondary generalization, are the main manifestation mode of this type of reflex epilepsies. Neurological examination and intercritical electroencephalography are usually normal, which may condition a delay in diagnosis, and the clinical suspicion is fundamental. Antiepileptic treatment is initiated when associated with another type of epilepsy or when certain simple measures, such as lowering the water temperature in the bath, do not control crises. Spontaneous disappearance is possible; when pharmacological therapy is necessary, there is usually a good response. We present the case of an infant diagnosed with hot-water epilepsy. Key words: seizures, reflex epilepsies, hot water-induced reflex epilepsy.
La epilepsia refleja por agua caliente es un tipo de convulsión poco frecuente cuya fisiopatología se desconoce. Estas crisis reflejas suelen iniciarse pocos segundos tras el contacto con el agua y, comúnmente, a temperaturas de 37-48 ºC. Los automatismos y las crisis parciales complejas, con o sin generalización secundaria, son el modo de manifestación principal. La exploración neurológica y el electroencefalograma intercrítico no suelen presentar alteraciones, lo que puede condicionar un retraso en el diagnóstico, por lo que es fundamental la sospecha clínica. El tratamiento antiepiléptico se inicia cuando se asocia a otro tipo de epilepsia o cuando ciertas medidas sencillas, como el descenso de la temperatura del agua en el baño, no controlan las crisis. Es posible la desaparición espontánea. Cuando es necesaria la terapéutica farmacológica, existe, normalmente, buena respuesta. Se presenta el caso de un lactante con diagnóstico de epilepsia refleja por agua caliente.
Assuntos
Epilepsia Reflexa/diagnóstico , Temperatura Alta/efeitos adversos , Água/efeitos adversos , Eletroencefalografia , Epilepsia Reflexa/etiologia , Humanos , Lactente , MasculinoRESUMO
As convulsões reflexas audiogênicas dos felinos são caracterizadas por crises reflexas desencadeadas essencialmente por estímulos sonoros, sendo pouco conhecida em animais de companhia. Objetivou-se relatar um caso de convulsão reflexa audiogênica em um felino. Foi atendido em um hospital, um felino, macho, de 19 anos com queixa de convulsão. Com base no relato da tutora, exclusão de outras enfermidades e avaliação da crise, diagnosticou-se convulsão reflexa audiogênica. Conclui-se que a experiência profissional do clínico associada a percepção da tutora foram essenciais para o diagnóstico.
Feline audiogenic reflex seizures are characterized by reflex seizures triggered essentially by sound stimuli, being little known in companion animals. This study aimed to report a case of audiogenic reflex seizure in a feline. He was seen at a hospital, a 19-year-old male feline with a seizure complaint. Based on the tutor's report, exclusion of other diseases and crisis assessment, an audiogenic reflex seizure was diagnosed. It was concluded that the professional experience of the clinician associated with the tutor's perception were essential for the diagnosis.
Assuntos
Animais , Gatos , Epilepsia Reflexa/diagnóstico , Epilepsia Reflexa/veterinária , Levetiracetam/uso terapêuticoRESUMO
As convulsões reflexas audiogênicas dos felinos são caracterizadas por crises reflexas desencadeadas essencialmente por estímulos sonoros, sendo pouco conhecida em animais de companhia. Objetivou-se relatar um caso de convulsão reflexa audiogênica em um felino. Foi atendido em um hospital, um felino, macho, de 19 anos com queixa de convulsão. Com base no relato da tutora, exclusão de outras enfermidades e avaliação da crise, diagnosticou-se convulsão reflexa audiogênica. Conclui-se que a experiência profissional do clínico associada a percepção da tutora foram essenciais para o diagnóstico.(AU)
Feline audiogenic reflex seizures are characterized by reflex seizures triggered essentially by sound stimuli, being little known in companion animals. This study aimed to report a case of audiogenic reflex seizure in a feline. He was seen at a hospital, a 19-year-old male feline with a seizure complaint. Based on the tutor's report, exclusion of other diseases and crisis assessment, an audiogenic reflex seizure was diagnosed. It was concluded that the professional experience of the clinician associated with the tutor's perception were essential for the diagnosis.(AU)
Assuntos
Animais , Gatos , Epilepsia Reflexa/diagnóstico , Epilepsia Reflexa/veterinária , Levetiracetam/uso terapêuticoRESUMO
Wistar Audiogenic Rat (WAR) strain is an animal model for epilepsy studies, the chronic multifactorial disease that affects millions of people worldwide. The animals of this strain are genetically predisposed to sound-induced seizures, called audiogenic seizures, and have been used for many years in studies to understand the mechanisms involved in the epilepsies and their neuropsychiatric comorbidities, as well as the screening of potential anti-convulsant agents. Nevertheless, little is known about the reproductive characteristics of these animals. The main goal of this study was to characterize the female reproductive performance and the fetal growth of WARs in comparison to the Wistar rats, obtaining important information for physiology and behavioral studies, as well as for the preservation of the strain. The results indicated few differences between WAR and Wistar regarding the female reproductive performance. There was no significant difference in the number of pregnant females by mating, number of live births per female, number of cells per blastocyst, and several characteristics related to reproductive performance, such as pre- and post-implantation losses. However, significant differences were observed in birth weight and weight gain until weaning, with WAR animals presenting a body weight below Wistar at birth and reduced body weight gain during the lactation period. In addition, the WAR females showed lower body weight on the day 20 of pregnancy and a larger number of corpora lutea, when compared with those of Wistar animals. Thus, we conclude that although Wistar and WAR strains have few differences in their reproductive performance, which might impact future physiological life challenges or others experimentally induced procedures, it still is a very viable strain regarding reproduction. Abbreviations: CONCEA: National Council for the Control of Animal Experimentation; GEPR: genetically epilepsy-prone rats; WAR: Wistar Audiogenic Rat.
Assuntos
Peso ao Nascer , Modelos Animais de Doenças , Epilepsia Reflexa , Prenhez , Animais , Blastocisto/citologia , Feminino , Desenvolvimento Fetal , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Ratos Wistar , Aumento de PesoRESUMO
The Wistar audiogenic rat (WAR) is an animal model of tonic-clonic epileptic seizures, developed after genetic selection by sister × brother inbreeding of Wistar rats susceptible to sound stimuli. Although metabolic changes have been described in this strain, nothing is known about its mitochondrial metabolism. Here, we addressed mitochondrial aspects of oxidative phosphorylation, oxidative stress, biogenesis, and dynamics in liver, skeletal muscle, and heart of male WARs and correlating them with physiological aspects of body metabolism. The results showed higher mitochondrial content, respiration rates in phosphorylation and noncoupled states, and H2O2 production in WARs. Liver presented higher content of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) and mammalian target of rapamycin, proteins related to mitochondrial biogenesis. In agreement, isolated liver mitochondria from WARs showed higher respiration rates in phosphorylation state and ADP-to-O ratio, as well as higher content of proteins related to electron transport chain ATP synthase, TCA cycle, and mitochondrial fusion and fission compared with their Wistar counterparts. Mitochondria with higher area and perimeter and more variable shapes were found in liver and soleus from WARs in addition to lower reduced-to-oxidized glutathione ratio. In vivo, WARs demonstrated lower body mass and energy expenditure but higher food and water intake and amino acid oxidation. When exposed to a running test, WARs reached higher speed and resisted for a longer time and distance than their Wistar controls. In conclusion, the WAR strain has mitochondrial changes in liver, skeletal muscle, and heart that improve its mitochondrial capacity of ATP production, making it an excellent rat model to study PGC1α overexpression and mitochondrial function in different physiological conditions or facing pathological challenges.
Assuntos
Epilepsia Reflexa/metabolismo , Trifosfato de Adenosina/biossíntese , Animais , Peso Corporal , Metabolismo Energético , Peróxido de Hidrogênio/metabolismo , Fígado/metabolismo , Masculino , Mitocôndrias Hepáticas/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Fosforilação Oxidativa , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/biossíntese , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Wistar , CorridaRESUMO
The Wistar Audiogenic Rat (WAR) is a model whose rats are predisposed to develop seizures following acoustic stimulation. We aimed to establish the transcriptional profile of the WAR model, searching for genes that help in understanding the molecular mechanisms involved in the predisposition and seizures expression of this strain. RNA-Seq of the corpora quadrigemina of WAR and Wistar rats subjected to acoustic stimulation revealed 64 genes differentially regulated in WAR. We validated twelve of these genes by qPCR in stimulated and naive (non-stimulated) WAR and Wistar rats. Among these, Acsm3 was upregulated in WAR in comparison with both control groups. In contrast, Gpr126 and Rtel1 were downregulated in naive and stimulated WAR rats in comparison with the Wistar controls. Qdpr was upregulated only in stimulated WAR rats that exhibited audiogenic seizures. Our data show that there are genes with differential intrinsic regulation in the WAR model and that seizures can alter gene regulation. We identified new genes that might be involved in the epileptic phenotype and comorbidities of the WAR model.
Assuntos
Epilepsia Reflexa/genética , Epilepsia Reflexa/patologia , Epilepsia Reflexa/fisiopatologia , Receptores Acoplados a Proteínas G/metabolismo , Teto do Mesencéfalo/fisiopatologia , Transcriptoma/fisiologia , Estimulação Acústica/efeitos adversos , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Excitação Neurológica/fisiologia , Masculino , Análise de Componente Principal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/genética , Espectrofotometria , Teto do Mesencéfalo/metabolismoRESUMO
Despite the many studies focusing on epilepsy, a lot of the basic mechanisms underlying seizure susceptibility are mainly unclear. Here, we studied cellular electrical excitability, as well as excitatory and inhibitory synaptic neurotransmission of CA1 pyramidal neurons from the dorsal hippocampus of a genetic model of epilepsy, the Wistar Audiogenic Rat (WARs) in which limbic seizures appear after repeated audiogenic stimulation. We examined intrinsic properties of neurons, as well as EPSCs evoked by Schaffer-collateral stimulation in slices from WARs and Wistar parental strain. We also analyzed spontaneous IPSCs and quantal miniature inhibitory events. Our data show that even in the absence of previous seizures, GABAergic neurotransmission is reduced in the dorsal hippocampus of WARs. We observed a decrease in the frequency of IPSCs and mIPSCs. Moreover, mIPSCs of WARs had faster rise times, indicating that they probably arise from more proximal synapses. Finally, intrinsic membrane properties, firing and excitatory neurotransmission mediated by both NMDA and non-NMDA receptors are similar to the parental strain. Since GABAergic inhibition towards CA1 pyramidal neurons is reduced in WARs, the inhibitory network could be ineffective to prevent the seizure-dependent spread of hyperexcitation. These functional changes could make these animals more susceptible to the limbic seizures observed during the audiogenic kindling.
Assuntos
Região CA1 Hipocampal/metabolismo , Epilepsia Reflexa/genética , Epilepsia/genética , Células Piramidais/metabolismo , Animais , Região CA1 Hipocampal/patologia , Modelos Animais de Doenças , Epilepsia/metabolismo , Epilepsia/patologia , Epilepsia Reflexa/patologia , Humanos , Células Piramidais/patologia , Ratos , Convulsões/genética , Convulsões/metabolismo , Convulsões/patologia , Sinapses/genética , Sinapses/patologia , Transmissão Sináptica/genética , Lobo Temporal/metabolismo , Lobo Temporal/patologiaRESUMO
There are reports of patients whose epileptic seizures are prevented by means of olfactory stimulation. Similar findings were described in animal models of epilepsy, such as the electrical kindling of amygdala, where olfactory stimulation with toluene (TOL) suppressed seizures in most rats, even when the stimuli were 20% above the threshold to evoke seizures in already kindled animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic seizures induced by acute acoustic stimulation, although it also expresses limbic seizures when repeated acoustic stimulation occurs - a process known as audiogenic kindling (AK). The aim of this study was to evaluate whether or not the olfactory stimulation with TOL would interfere on the behavioral expression of brainstem (acute) and limbic (chronic) seizures in the WAR strain. For this, animals were exposed to TOL or saline (SAL) and subsequently exposed to acoustic stimulation in two conditions that generated: I) acute audiogenic seizures (only one acoustic stimulus, without previous seizure experience before of the odor test) and II) after AK (20 acoustic stimuli [2 daily] before of the protocol test). We observed a decrease in the seizure severity index of animals exposed only to TOL in both conditions, with TOL presented 20s before the acoustic stimulation in both protocols. These findings were confirmed by behavioral sequential analysis (neuroethology), which clearly indicated an exacerbation of clusters of specific behaviors such as exploration and grooming (self-cleaning), as well as significant decrease in the expression of brainstem and limbic seizures in response to TOL. Thus, these data demonstrate that TOL, a strong olfactory stimulus, has anticonvulsant properties, detected by the decrease of acute and AK seizures in WARs.
Assuntos
Estimulação Acústica , Excitação Neurológica/fisiologia , Sistema Límbico/fisiologia , Convulsões , Olfato/efeitos dos fármacos , Tolueno/farmacologia , Tonsila do Cerebelo , Animais , Tronco Encefálico , Modelos Animais de Doenças , Epilepsia Reflexa , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To test the hypothesis that naive Wistar audiogenic rats (WARs) display erectile dysfunction (ED), which is associated with increased sympathetic-mediated contractile tone and decreased nitric oxide-mediated relaxation responses of the cavernous tissue. METHODS: Changes in the ratio of the maximal intracavernosal pressure-mean arterial pressure after the electrical stimulation of the right major pelvic ganglion were determined in vivo. Cavernosal contractility was induced by electrical field stimulation and phenylephrine. In addition, nonadrenergic-noncholinergic (NANC)-induced relaxation was determined. Rho-kinase (ROCK) pathway proteins, neuronal nitric oxide synthase (nNOS) protein expression, and endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 activities were determined by Western blot. RESULTS: WARs display a significant decrease in maximal intracavernosal pressure-mean arterial pressure responses suggesting ED in this strain. Sympathetic-mediated contractile responses were increased in WARs and contractile responses to phenylephrine were not changed. The increased sympathetic-mediated contractile responses were not associated with changes in the ROCK pathway. On the other hand, NANC-mediated relaxation responses were significantly reduced in WARs. This functional response was accompanied by decreased nNOS and total eNOS protein expressions, augmented phosphorylated eNOS, and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels. CONCLUSION: Our data have demonstrated that naive WARs display ED in vivo that is associated with increased sympathetic-mediated contractile responses and decreased NANC-mediated relaxation responses. The increase in contractile responses is independent of the ROCK pathway, and the changes in relaxation responses are associated with a decrease in nNOS protein expression, which may activate compensatory mechanisms in the cavernous tissue.
Assuntos
Epilepsia Reflexa/complicações , Disfunção Erétil/fisiopatologia , Óxido Nítrico Sintase Tipo I/biossíntese , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Animais , Western Blotting , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Disfunção Erétil/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Accumulating evidence from different animal models has contributed to the understanding of the bidirectional comorbidity associations between the epileptic condition and behavioral abnormalities. A strain of animals inbred to enhance seizure predisposition to high-intensity sound stimulation, the Wistar audiogenic rat (WAR), underwent several behavioral tests: forced swim test (FST), open-field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), social preference (SP), marble burying test (MBT), inhibitory avoidance (IAT), and two-way active avoidance (TWAA). The choice of tests aimed to investigate the correlation between underlying circuits believed to be participating in both WAR's innate susceptibility to sound-triggered seizures and the neurobiological substrates associated with test performance. Comparing WAR with its Wistar counterpart (i.e., resistant to audiogenic seizures) showed that WARs present behavioral despair traits (e.g., increased FST immobility) but no evidence of anhedonic behavior (e.g., increased sucrose consumption in SPT) or social impairment (e.g., no difference regarding juvenile exploration in SP). In addition, tests suggested that WARs are unable to properly evaluate degrees of aversiveness (e.g., performance on OFT, EPM, MBT, IAT, and TWAA). The particularities of the WAR model opens new venues to further untangle the neurobiology underlying the co-morbidity of behavioral disorders and epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
Assuntos
Estimulação Acústica/efeitos adversos , Aprendizagem da Esquiva , Modelos Animais de Doenças , Epilepsia Reflexa/psicologia , Predisposição Genética para Doença/psicologia , Convulsões/psicologia , Animais , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Suscetibilidade a Doenças/psicologia , Epilepsia Reflexa/genética , Epilepsia Reflexa/fisiopatologia , Predisposição Genética para Doença/genética , Masculino , Aprendizagem em Labirinto/fisiologia , Ratos , Ratos Wistar , Convulsões/genética , Convulsões/fisiopatologiaRESUMO
PURPOSE: Juvenile myoclonic epilepsy (JME) is a heterogeneous syndrome in which seizures can be precipitated not only by non-specific factors, such as sleep deprivation and stress, but also by specific stimuli, such as photic stimuli, eye-closure, praxis, and language. The presence of these reflex traits may indicate the hyperexcitability of different cortical areas, which may be reflected in patients' neuropsychological deficit profile. The objective of our study is to investigate the possible relations between JME endophenotypes and patients' cognitive performance. METHODS: 61 JME patients were divided into four groups: no reflex traits (group 1, 20 patients); praxis induction (group 2, 13); eye-closure and/or photosensitivity (group 3, 17); and a combination of different reflex traits (group 4, 11). Neuropsychological performance was compared between JME subgroups. 60 healthy controls were used to calculate z-scores. Patients also underwent psychiatric assessment. We controlled the clinical variables, e.g. age at epilepsy onset, frequency of myoclonic seizures, total and sedative drug load, setting them as covariables for the ANOVA analysis. RESULTS: Praxis induction was more common in males (p=0.018) and groups with reflex traits (2, 3, and 4) presented higher rates of persistent myoclonia, polytherapy, clonazepam use (group 3), and more frequent psychiatric comorbidities. Group 4 patients performed worse in Trail Making Test B than the patients in group 1. These findings were independent of clinical variables. CONCLUSION: JME patients with a combination of praxis induction and eye-closure/photosensitivity had greater executive dysfunction, revealing an association between reflex ictogenic mechanisms and cognitive performance.
Assuntos
Disfunção Cognitiva/fisiopatologia , Endofenótipos , Epilepsia Reflexa/fisiopatologia , Função Executiva/fisiologia , Epilepsia Mioclônica Juvenil/fisiopatologia , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Disfunção Cognitiva/etiologia , Epilepsia Reflexa/complicações , Epilepsia Reflexa/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/complicações , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Fatores Sexuais , Adulto JovemRESUMO
INTRODUCTION: We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy. METHODS: Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurements, and body temperature (Tb) measurements were taken via temperature sensors implanted in the abdominal cavities of the animals. RESULTS: No significant difference was observed between the WAR and Wistar control group with respect to the thermoregulatory response elicited by exposure to both acute hypercapnia and acute hypoxia (p>0.05). However, we found that the VE of WARs was attenuated relative to that of Wistar control animals during exposure to both hypercapnic (WAR: 133 ± 11% vs. Wistar: 243 ± 23%, p<0.01) and hypoxic conditions (WAR: 138 ± 8% vs. Wistar: 177 ± 8%; p<0.01). In addition, we noted that this ventilatory attenuation was followed by alterations in the behavioral responses of these animals. CONCLUSIONS: Our results indicate that WARs, a genetic model of epilepsy, have important alterations in their ability to compensate for changes in levels of various arterial blood gasses. WARs present an attenuated ventilatory response to an increased PaCO2 or decreased PaO2, coupled to behavioral changes, which make them a suitable model to further study respiratory risks associated to epilepsy.