Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks / Consumo de peixe, contaminantes e morte súbita em epilepsia: mais benefícios do que riscos

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.

Seizure occurrence in patients with chronic renal insufficiency in regular hemodialysis program

Hemodialysis-associated seizure is a complication of hemodialysis. This report describes the occurrence of seizures in patients with end stage renal disease on dialysis therapy at the Nephrology Institute of Mogi das Cruzes, São Paulo State, Brazil. A retrospective medical history of 189 patients was reviewed to investigate the occurrence of convulsive seizures during dialytic program. Seven patients with history of seizures were selected but five of them were included in our study. Three patients presented generalized tonic-clonic seizures, one had partial seizure with secondary generalization, and one presented unclassified seizure. Three patients presented seizure just during the dialysis (unique seizure) and one of them presented convulsive status epilepticus. The two other patients had already presented seizures prior the beginning of dialysis. We conclude that seizures in renal failure could be considered as occasional events that do not usually become chronic.

Convulsões durante o tratamento dialítico podem constituir uma complicação da hemodiálise. Esse artigo descreve a ocorrência de crises em pacientes em estágio final de insuficiência renal crônica sob tratamento dialítico no Instituto de Nefrologia de Mogi das Cruzes, São Paulo, Brasil. Foram revistos os prontuários de 189 pacientes, com o objetivo de investigar a ocorrência de crises convulsivas durante o tratamento dialítico. Dos sete pacientes selecionados com história de crises, cinco concordaram em participar de nosso estudo. Três pacientes apresentaram crises generalizadas tônico-clônicas, um apresentou crise parcial com generalização subseqüente e um apresentou crise inclassificada. Três pacientes apresentaram crises apenas durante o processo dialítico (crise única) sendo que um deles apresentou status epilepticus convulsivo. Os outros dois pacientes já haviam apresentado crises antes do início do tratamento dialítico. Nós concluímos que as crises convulsivas que ocorrem em pacientes com falência renal podem ser consideradas como eventos ocasionais e que usualmente não se tornam crônicas.

Absence-like seizures in adult rats following pilocarpine-induced status epilepticus early in life

Administration of pilocarpine causes epilepsy in rats if status epilepticus (SE) is induced at an early age. To determine in detail the electrophysiological patterns of the epileptogenic activity in these animals, 46 Wistar rats, 7-17 days old, were subjected to SE induced by pilocarpine and electro-oscillograms from the cortex, hippocampus, amygdala, thalamus and hypothalamus, as well as head, rostrum and vibrissa, eye, ear and forelimb movements, were recorded 120 days later. Six control animals of the same age range did not show any signs of epilepsy. In all the rats subjected to SE, iterative spike-wave complexes (8.1 ± 0.5 Hz in frequency, 18.9 ± 9.1 s in duration) were recorded from the frontal cortex during absence fits. However, similar spike-wave discharges were always found also in the hippocampus and, less frequently, in the amygdala and in thalamic nuclei. Repetitive or single spikes were also detected in these same central structures. Clonic movements and single jerks were recorded from all the rats, either concomitantly with or independently of the spike-wave complexes and spikes. We conclude that rats made epileptic with pilocarpine develop absence seizures also occurring during paradoxical sleep, showing the characteristic spike-wave bursts in neocortical areas and also in the hippocampus. This is in contrast to the well-accepted statement that one of the main characteristics of absence-like fits in the rat is that spike-wave discharges are never recorded from the hippocampal fields.

Behavioral and electroencephalographic analysis of seizures induced by intrahippocampal injection of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera

In this study, the behavioral and electroencephalographic (EEG) analysis of seizures induced by the intrahippocampal injection in rats of granulitoxin, a neurotoxic peptide from the sea anemone Bunodosoma granulifera, was determined. The first alterations occurred during microinjection of granulitoxin (8 µg) into the dorsal hippocampus and consisted of seizure activity that began in the hippocampus and spread rapidly to the occipital cortex. This activity lasted 20-30 s, and during this period the rats presented immobility. During the first 40-50 min after its administration, three to four other similar short EEG seizure periods occurred and the rats presented the following behavioral alterations: akinesia, facial automatisms, head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements. Within 40-50 min, the status epilepticus was established and lasted 8-12 h. These results are similar to those observed in the acute phase of the pilocarpine model of temporal lobe epilepsy and suggest that granulitoxin may be a useful tool not only to study the sodium channels, but also to develop a new experimental model of status epilepticus.

Catecholamine response to exercise in individuals with different levels of paraplegia

The purpose of this study was to investigate the effect of the level of injury on the serum level of norepinephrine (Nor) and epinephrine (Epi) at rest and after maximal exercise in individuals with paraplegia. Twenty-six male spinal cord-injured subjects with complete paraplegia for at least 9 months were divided into two groups of 13 subjects each according to the level of injury, i.e., T1-T6 and T7-T12. Serum Nor and Epi concentrations were measured by HPLC-ECD, at rest (PRE) and immediately after a maximal ergospirometric test (POST). Statistical analysis was performed using parametric and non-parametric tests. Maximal heart rate, peak oxygen uptake, and PRE and POST Nor were lower in the T1-T6 than in the T7-T12 group (166 Ý 28 vs 188 Ý 10 bpm; 18.0 Ý 6.0 vs 25.8 Ý 4.1 ml kg-1 min-1; 0.54 Ý 0.26 vs 0.99 Ý 0.47 nM; 1.48 Ý 1.65 vs 3.07 Ý 1.44 nM). Both groups presented a significant increase in Nor level after exercise, while only the T7-T12 group showed a significant increase in Epi after exercise (T1-T6: 0.98 Ý 0.72 vs 1.11 Ý 1.19 nM; T7-T12: 1.24 Ý 1.02 vs 1.89 Ý 1.57 nM). These data show that individuals with paraplegia above T6 have an attentuated catecholamine release at rest and response to exercise as compared to subjects with injuries below T6, which might prevent a better exercise performance in the former group

Neuromodulin (GAP-43): a protein related to chronic diseases

The important of a large number of proteins involved in chronic diseases has been reported. In the present study the phosphoprotein GAP-43 was focused due to its relationship with chronic diseases such as epilepsy Alzheimer's disease, cerebral ischemia and phusiological events like long-term potentiation (LTP).

Effect of an aerobic exercise program on blood pressure and catecholamines in normotensive and hypertensive subjects

Interrelations between physical exercise, monoamines and hypertension are postulated by various investigators. The purpose of the present study was to determine and compare catecholamine levels at rest and after a 12-week aerobic exercise program in 11 sedentary normotensive (N) and 8 hypertensive (H) men. Plasma catecholamines were determined by high performance liquid chromatography with electrochemical detection. A significant post-exercise increase in plasma noradrenaline was observed in the N and H groups (P<0.01) both before and after the aerobic exercise program. The hypertensive group showed a significant reduction of the sum of 7 skinfold thickness scores after the aerobic exercise program (from 178.7 ñ 65.6 to 144.0 ñ 47.4 mm) although no significant difference was observed when the body mass index was compared. A significant reduction in diastolic blood pressure at rest was observed in the H group after the aerobic exercise program (from 99.2 ñ 2.0 to 85.0 ñ 5.5). There were no significant differences in catecholamine concentrations between groups before and after the 12-week aerobic exercise program at rest and post-exercise. These data show a relationship between physical exercise and hypertension that was not related to changes in plasma catecholamine levels.

Serotonina sérica e síndrome de Rett / Serum serotonin and Rett syndrome

A síndrome de Rett, uma patologia neurodegenerativa que afeta meninas, caracteriza-se por uma involuçäo neuropsicomotora do desenvolvimento. Sendo o diagnóstico desta síndrome exclusivamente clínico, o presente trabalho teve como objetivo o estudo do conteúdo de serotonina sérica em crianças normais e portadoras da síndrome de Rett. A metodologia empregada para a quantificaçäo de 5HT no soro foi a cromatografia líquida de alta eficiência acoplada a detecçao eletroquímica. Os resultados obtidos mostraram uma hiperserotonemia em 81 por cento das crianças com síndrome de Rett. Verificou-se também uma correlaçäo positiva entre níveis altos de serotonina no soro e a deambulaçäo independente, mostrando que pacientes sem marcha voluntária apresentam níveis séricos maiores deste neurotransmissor. O presente trabalho sugere que o nível sérico de serotonina pode vir a ser usado como um possível marcador biológico no diagnóstico de estadiamento da síndrome de Rett.

Increased serotonin levels in physically trained men

It has been postulated that exercise training influences monoaminergic systems. The purpose of the present study was to determine the basal level of serum serotonin (5HT) in track and field-trained men (N = 15) and in untrained subjects matched by age, weight and height (N = 15). Serum serotonin levels were determined in blood drawn into dry tubes after a 12-h fast by high performance liquid chromatography utilizing electrochemical detection. Mean (+/- SD) serum serotonin levels were: 141.32 +/- 38.77 ng/ml for trained subjects and 97.77 +/- 30.53 ng/ml for untrained subjects (P < 0.01, Student t-test). These data show that basal serum serotonin levels are increased by exercise training.

Serum serotonin levels of normal and autistic children

1. Serum serotonin (5HT) was determined in normal and autistic children by high performance liquid chromatography with electrochemical detection (HPLC-ED), after serum deproteinization. 2. The sample deproteinization was carried out by the addition of 3.4 M HCLO4 to a small volume of the serum, followed by freezing, centrifugation, dilution and injection of sample into the HPLC. 3. Serum 5HT concentration was significantly increased in autistic children (303 +/- 92 ng/ml) (N = 19) when compared to that of normal children (215 +/- 67 ng/ml) (N = 46). The data of normal children analyzed by ANOVA for sex or age showed no difference. 4. The method employed in this study showed high resolution, good sensitivity and can be used for routine determination of serum 5HT in the clinical investigation of hyperserotonemia in autism

Serum catecholamine levels determined by high performance liquid chromatography coupled with electrochemical detection

Este trabalho apresenta um método rápido para a quantificaçäo de catecolaminas utilizando a técnica de cromatografia líquida de fase reversa acoplada à detecçäo eletroquímica. Separaçäo isocrática rápida foi obtida empregando como fase móvel a soluçäo: 0,02M de fosfato de sódio dibásico, 0,02M de ácido nítrico, pH 2,64, metanol a 10 por cento, 0,12mM de EDTA sódico e 556 mg/L de ácido heptanosulfônico. Delineou-se o procedimento de preparaçäo das amostras com extraçäo das monoaminas em alumina, para melhorar a recuperaçäo e diminuir fatores de diluiçäo. O tempo total de análise é de 15 minutos, com boa separaçäo dos picos de monoaminas. O limite de detecçäo obtido para as monoaminas séricas é de 40 a 50 pg/mL, com uma taxa de recuperaçäo de 70-75 por cento.

Implante de células embrionárias em um modelo experimental de epilepsia / Embryons cells implanted in a experimental model of epilepsy

Estudos experimentais mostram que celulas nervosas provenientes de embriöes säo capazes de sobreviver, em diversas regiöes do SNC de animais adultos. Uma vez integrados ao hospedeiro, esses neurônios podem liberar neurotransmissores específicos em regiöes previamente desnervadas. Essa abordagem oferece a possibilidade de se restabelecer a neurotransmissäo, em patologias nervosas diversas, particularmente as degenerativas. Resultados bastantes favoráveis têm sido obtidos utilizando modelos experimentais de patologias extrapiramidais e quadros demenciais. Em epileptologia, no entanto, resultados favoráveis e desfavoráveis têm sido encontrados. Uma das razöes para a ocorrência de dados conflitantes pode estar relacionada a escolha de modelos experimentais, que nem sempre reproduzem os mesmos fenômenos fisiopatológicos. O objetivo deste trabalho é o de avaliar o efeito do implante de células embrionárias noradrenérgicas sobre um modelo de crises espontâneas no rato. Neste modelo, as crises espontâneas säo observadas após a induçäo de status epilepticus através da administraçäo sistêmica de pilocarpina. Estudos realizados têm indicado ser este modelo muito semelhante às crises parciais complexas humanas associadas a escleose mesial temporal. Células embrionárias provenientes do locus coeruleus foram implantadas no hipocampo de animais epilépticos, sendo os animais acompanhados por 3 meses. A avaliaçäo histológica (imunohistoquímica para tirosina hidroxilase), 90 dias após o implante, demonstrou a presença de neurônios noradrenérgicos em várias regiöes do hipocampo. No entanto, o procedimento näo interferiu na freqüência de crises. Estes resultados diferem de estudos utilizando outros modelos animais, onde o mesmo tipo de transplante apresentou efeito positivo e indicam que, no modelo da pilocarpina, é provável que outros sistemas neurotransmissores estejam envolvidos, além da simples participaçäo isolada do sistema noradrenérgico

Some evidence that intrahippocampal grafting of noradrenergic neurons suppresses spontaneous seizures in epileptic rats

Pilocarpine-induced status epilepticus leads to widespread limbic forebrain damage in rats and provides a model for studying intractable epilepsy. Noradrenergic neurons in suspension, prepared from the locus coeruleus region of donors on the 13th or 14th gestational day, were microinjected bilaterally into the hippocampus (8 rats) and into the cerebellum (4 rats) or the olfactory bulb (4 rats) of epileptic rats. Three µ1 of suspension was deposited at the rat of 1 µl/min. Control animals were not submitted to surgery (4 rats). After six weels a marked reduction of suppression of spontaneous seizures was observed in intrahippocampally grafted rats. from these preliminary results we suggest that frafts can be used to suppress spontaneous recurrent epleptic seizures

Bilateral microinjection of ethosuximide into the substantia nigra does not prevent amygdala-kindled seizures

Male Wistar rats were sugjected to daily sessions of electrical amygdala kindling until a generalized seixure was observed on five consecutive days. Bilateral microinections (0.5 micronl) of ethosuximide (ETX) (10 pg/micronl) or saline were then administered though guide cannulas into the substantia nigra (pars reticulata). No significant difference was observed between the ETX (N = 8) and saline (N = 8) groups in duration of afterdischarge or in the latency for stage 5 generalized seizures. Our results indicate that ETX applied to the substantia nigra is not effective in suppressing amydala-kindled seizure

HPLC determination of norepinephrine, 5-hydroxytyramine and 5-hydroxytryptamine in rat brain using sodium dodecyl sulphate as ion-pair

1. A simple HPLC method using sodium dodecyl sulfate (SDS) and elelctrochemical detection for the determination of norepinephrine (NE), 5-hydroxytyramine (DA) and 5-hydroxytryptamine (5-HT) in brain regions is described. 2. the tissue extraction procedure involved only two stepes: protein precipitation with perchloriac acid and pH adjustment to near 3.0. When used in combination with methanol as ion-pair in the mobile phase, sodium dodecyl sulgate effectively separated NE (6.6 min), epinephrine (EPI), 7.9 min), DA (14.3 min) and 5-HT (29.5 min) and the high methanol concentration used prevente the overlapping of the metabolites and monoamines in their chromatographic peaks. 3. the method was sensitive (40 to 70 pg of monoamine can be quantified) and reproducible and the values obtained for cortex, hippocampus, striatum and substantia nigra were consoant with most literature data

GAD-immunoreactive neurons are preserved in the hippocampus of rats with spontaneous recurrent seizures

In the present glutamate decarboxylase immunoreactivity (GAD-IR) was used to quantify GABAergic neurons in the hippocampus of rats exhibiting spontaneous recurtent seizures following pilocarpine-induced status epilepticus. Histological examination demonstrated marked neuronal damage to hippocampal neurons. However, in the same region, GAD-IR neurons were preserved. the present data demonstrate a selective resistance of GABAergic neurons to status epilepticus-induced neuronal damage, suggesting that loss of hippocampal GABAergic neurons does not underlie the recurrence of seizures in these animals

Protective effect of short-term post-ischemic hypothermia on the gerbil brain

1. The effects of post-ischemic hypothermia were studied in the gerbil brain. After 5 min of bilateral common carotid occlusion (BCCO) under thiopental anesthesia and normothermia (rectal temperature of 37 ñ 0.5-C) 20,animals were maintained either normothermic (group NT, N = 10) or hypothermic (rectal temperature of 29 ñ 0.5-C, obtained within 5 min of carotid recirculation) for 5h (group HT, N = 10). Sham-operated animals (N = 5) were kept normothermic for 5h following the surgical procedure. 2. After a 7-day period of survival, damage to the dorsal hippocampus was determined histopathological by cresyl - violet staining and graded on a scale of 0 to 3. The histopathological damage observed in the CAI subfield of the hippocampus was found to be more intense in NT than in HT gerbils (P < 0.001, Mann-Whitney U-test). 3. Those results suggest that moderate and short-lasting hypothermia induced early in the recirculation period protects the brain against ischemic injury. The importance of these results is discussed in terms of pathophysiology, tratment and interpretation of experimental brain ischemia data

Learning impairment in chronic epileeptic rats following pilocarpine-induced status epilepticus

Male Wistar rats were subjected to pilocarpine-induced status epilepticus and allowed to recor. After reaching the chronic state with spontaneous seizures they were tested in an 8-arm radial maze. during learning trials, epileptic rats made significantly more errors than controls. Even in the last trials epileptic rats did not improve their performance, indicating severe learning disability. These results suggest that spontaneous seizures after pilocarpine-induced status epilepticus are a useful model for studying the learning and memory detected in some cases of symptomatic epilepsy

Effect of amygdaloid kindled seizures during pregnancy on neonatal brain biogenic amines

The effects of amygdaloid kindled seizures during pregancy on the concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5HT) and of their repective metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), homovanilic acid (HVA) and 5-hydroxy-indoleacetic acid (5HIAA), have been studied in the cerebral cortex, brain stem and cerebellum of rat offspring at bith. The levels of DA and NE were invreased and those of HVA and MHPG wee not modified in the cortex. The levels of DA, NE, 5HT, MHPG and 5HIAA were increased in the cerebellum. The brain stem presented a decrease in DA and 5HT levels, but increased MHPG and HVA levels. It is suggested that, in order to investigate possible changes in the biogenic amine loevels on the postnatal period, carefully planned prospective studies are needed