RESUMO
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
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
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: Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. METHODS: We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. RESULTS: Basal RR interval (RRi) was similar between WAR and Wistar rats (188 ± 5 vs 199 ± 6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92 ± 3 vs 115 ± 5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2 ± 0.6 vs 5.6 ± 1 mmHg) and volume (137 ± 9 vs 68 ± 9 µL) as well as lower rate of increase in ventricular pressure (5266 ± 602 vs 7320 ± 538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014 ± 780 vs -7766 ± 998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078 ± 0.011 vs 0.036 ± 0.011 mmHg.µL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. CONCLUSIONS: The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy.
Assuntos
Estimulação Acústica/efeitos adversos , Doenças Cardiovasculares/etiologia , Modelos Animais de Doenças , Epilepsia Reflexa/complicações , Disfunção Ventricular Esquerda/etiologia , Animais , Pressão Sanguínea , Doenças Cardiovasculares/patologia , Eletrocardiografia , Epilepsia Reflexa/patologia , Frequência Cardíaca , Masculino , Ratos , Ratos Mutantes , Ratos Wistar , Fatores de Risco , Disfunção Ventricular Esquerda/patologiaRESUMO
PURPOSE: Cardiac dysfunction is one of the possible causes of sudden unexpected death in epilepsy (SUDEP). Therefore, the objective of this study was to evaluate cardiac and electrocardiographic parameters in rats with audiogenic epileptic seizures (WAR--Wistar audiogenic rats). METHODS: In vivo arterial pressure, heart rate (HR), autonomic tone and electrocardiography (ECG) were measured in awake animals in order to examine cardiac function and rhythm. Ex vivo, the Langendorff technique was used to analyze the cardiac function and the severity of reperfusion arrhythmias. In vitro, confocal microscopy was used to evaluate calcium transient parameters of isolated ventricular cardiomyocytes. RESULTS: In vivo autonomic tone evaluation revealed enhanced sympathetic activity, changes in cardiac function with increased systolic arterial pressure and higher basal HR in WAR. In addition, ECG analysis demonstrated electrical alterations with prolongation of the QT interval and QRS complex in these animals. Ex vivo, we observed a decrease in systolic tone and HR and an increase in the duration of ischemia/reperfusion arrhythmias in WAR. Moreover, intracellular Ca2+ handling analysis revealed an increase in the peak of calcium and calcium transient decay in audiogenic rats. Treatment with atenolol (ß1-adrenergic antagonist) normalized the systolic tone, reduced cardiac hypertrophy and the associated increase in the susceptibility to reperfusion arrhythmias observed in WAR. CONCLUSION: We present evidence that chronic disturbances in sympathetic tone in WAR cause increases the risk to life-threatening arrhythmias. Our results support a relationship between seizures, cardiac dysfunction and cardiac arrhythmias, which may contribute to the occurrence of SUDEP.
Assuntos
Estimulação Acústica/efeitos adversos , Arritmias Cardíacas/fisiopatologia , Epilepsia Reflexa/fisiopatologia , Convulsões/fisiopatologia , Animais , Arritmias Cardíacas/complicações , Pressão Sanguínea/fisiologia , Eletrocardiografia/métodos , Epilepsia Reflexa/complicações , Frequência Cardíaca/fisiologia , Masculino , Ratos , Ratos Wistar , Convulsões/complicaçõesRESUMO
UNLABELLED: Intermittent photic stimulation (IPS) may produce epileptiform discharges and seizures, most of which are generalized. There are several cases of focal seizures of occipital origin induced by IPS and only five reported cases originating from the temporal lobe (TL). We report an unusual case of TL epilepsy, supported by electroclinical and neuroimaging data, with rhythmic focal TL discharges precipitated by photic stimulus. CASE REPORT: A 37 year old male with refractory epilepsy due to a right mesial temporal sclerosis presented a focal right TL photoparoxysmal response during IPS. A routine, interictal SPECT study obtained with injection of HMPAO, carried out during continuous pulses of the photic stimulus at 16 Hz, disclosed hyperperfusion over the right TL. Presurgical ictal studies demonstrated seizures arising from the same region. A temporal lobectomy rendered the patient seizure-free and further EEGs with IPS were normal. CONCLUSION: To our knowledge, this is the sixth case in medical literature showing evidence of photosensitivity associated with a TL lesion and it is the first in which photic stimulation induced a focal electrographic response of the involved TL. We hypothesize that in rare cases, photosensitivity may be related to a mesial TL lesion without occipital cortex involvement.