PubMed Health⌕ Search

Biomedical subjects

E A Cavalheiro

Publications and source records attributed to E A Cavalheiro.

At least 73 records · Page 4Linked to original sources
PubMed1992

Age-related anticonvulsant activity of NMDA in the rat caudate-putamen.

Striatal pathways are important for modulating the threshold for seizures in the rat forebrain. N-Methyl-D-aspartate (NMDA), an excitatory amino acid derivative and powerful anticonvulsant agent, when injected into the brain, has been shown to protect adult rats against kindling and pilocarpine-induced seizures when injected into the caudate-putamen. The present study examines whether the anticonvulsant action of NMDA in the caudate-putamen varies with age. Bilateral striatal administration of NMDA was effective in suppressing bicuculline-induced seizures in rats older than 23 days of age. The results suggest that striatal pathways involved in the anticonvulsant activity of NMDA in the caudate-putamen are not functionally active in developing rats before the 4th week of life.

Aging↗
PubMed1992

The relationships between neuronal activity and behavioral seizures induced by Palicourea marcgravii in rats.

To characterize the convulsions induced by an aqueous extract of Palicourea marcgravii (Pm), male Wistar rats were injected sc with 3.75 g/kg of the extract, and electroencephalogram and behavior were observed for periods up to 180 min after the Pm injections. Sleep spindles and generalized convulsive seizures were observed following Pm administration. Spiking activity was detected in both cortical and hippocampus recordings. They lasted approximately 2 min and were followed by a period of postical depression and/or death. These results agreed with previous behavioral experiments which suggested the toxic effect of Pm aqueous extract was mainly at the central nervous system level.

Animals↗
PubMed1991

Transient occlusion of rat carotid arteries decreases susceptibility to pilocarpine seizures.

Bilateral clamping of the carotid arteries (BCCA) for 24 min protects animals against convulsive effects of intraperitoneal injection of 300 mg/kg of pilocarpine when administered 14 days after surgery. Electrographic recordings from hippocampus, frontal cortex, striatum and substantia nigra demonstrate that (1) no spontaneous spiking activity is caused by the BCCA when observed for up to 10 days after surgery, (2) spiking activity can only be recorded in limbic structures but not in the frontal cortex after systemic administration of pilocarpine. These observations suggest that the propagation of seizure activity from subcortical limbic structures to the neocortex is affected by BCCA.

Animals↗
PubMed1991

Paradoxical anticonvulsant activity of the gamma-aminobutyrate antagonist bicuculline methiodide in the rat striatum.

Bicuculline methiodide (BMI), a gamma-aminobutyrate (GABA) antagonist, is a powerful convulsant agent when injected into the cerebral ventricles, amygdala, hippocampus, thalamus, neocortex, and deep prepiriform cortex in rats. In contrast, bilateral microinjection of BMI into the rat striatum confers protection against seizures induced by the cholinergic agonist pilocarpine (380 mg/kg, i.p.), with an ED50 of 94 fmol (range 45-195 fmol). No topographical variation in the anticonvulsant action of BMI was detected throughout rostrocaudal and dorsoventral aspects of the striatum. The anticonvulsant action of BMI in the striatum was reversed by coadministration of the GABA agonist muscimol or by blocking GABA-mediated inhibition in either the substantia nigra pars reticulata or in the entopeduncular nucleus. The results show that blockade of GABA-mediated inhibition in the striatum has a powerful anticonvulsant effect in the pilocarpine model, suggesting that GABAergic transmission in the striatum modulates the seizure propagation in the forebrain.

Animals↗
PubMed1991

Seizures induced by aminooxyacetic acid in mice: pharmacological characteristics.

Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 mumols (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97;150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L-Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D-glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid. The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug.

Aminooxyacetic Acid↗
PubMed1991

Effects of bilateral clamping of carotid arteries on hippocampal kindling in rats.

Moderate reduction of cerebral blood flow by bilateral clamping of carotid arteries (BCCA) in pentobarbital anaesthetized Wistar rats induces decreased PO2 and temperature values in vulnerable brain structures such as hippocampus and frontal cortex during the acute phase of clamping. Up to two weeks chronic increased GABA contents in hippocampus, substantia nigra and frontal cortex could be observed. During this time the development of hippocampal kindling was difficult. These results demonstrated an acute and chronic influence of GABA on most vulnerable brain structures which, however, do not lead to ischemic impacts as histological analyses demonstrate.

Animals↗
PubMed1991

Effects of systemic glucose injection on the development of amygdala kindling in rats.

The effects of systemic glucose administration on the development of electric amygdaloid kindling seizures were examined in Wistar rats. Daily intraperitoneal injections of glucose 100 mg/kg, 20 min prior to each amygdaloid stimulation did affect the rate of kindling development in comparison with the saline-injected group. The number of stimulations required to reach stage 5 was lower in animals treated with glucose. The facilitation of kindling development found in glucose-treated rats is related to a specific decrease in the number of stimulations needed to evolve from stage 2 to stage 3. These results indicate that systemic glucose administration facilitates amygdaloid kindling in rats.

Amygdala↗
PubMed1990

Substantia nigra regulates action of antiepileptic drugs.

The cholinergic agonist pilocarpine triggers sustained limbic seizures in rodents. Pilocarpine seizures were blocked by systemic administration of benzodiazepines, barbiturates, valproate and trimethadione, while diphenylhydantoin did not affect, and ethosuximide increased the susceptibility of rats to such seizures. This pattern of action of antiepileptic drugs is characteristic for pilocarpine seizures and different from other rodent models of epilepsy. Although the anatomical substrates in the forebrain involved in the expression of anticonvulsant activity are unknown, the basal ganglia are believed to be essential for the motor expression of pilocarpine seizures. Bilateral microinjections into the substantia nigra, a major output station of the basal ganglia, of midazolam (ED50 38.5 nmol; range 29-52 nmol), phenobarbital (ED50 16 nmol; range 7-39 nmol) and trimethadione (ED50 30 nmol; range 16-56 nmol) protected rats against pilocarpine seizures (380 mg/kg i.p.) Diphenylhydantoin (up to 100 nmol) remained inactive, while ethosuximide (ED50 38 nmol; range 22-65.5 nmol) reduced the threshold for pilocarpine seizures, converting subconvulsant doses of pilocarpine (200 mg/kg i.p.) into convulsant ones. The profiles of action of antiepileptic drugs on pilocarpine seizures were similar following intranigral and systemic administration. These observations suggest that the substantia nigra may mediate some actions of antiepileptic drugs.

Animals↗
PubMed1990

Dopamine control of seizure propagation: intranigral dopamine D1 agonist SKF-38393 enhances susceptibility to seizures.

The involvement of dopamine (DA) in human and experimental epilepsy has been discounted as DAergic drugs have little effect on convulsions. This work presents evidence that bilateral microinjection of the DAD1 agonist SKF-38393 into the substantia nigra enhances the susceptibility of rats to seizures, with an ED50 of 20 pmol (range 13-31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones. The proconvulsant action of SKF-38393 was reversed by blocking D1-mediated transmission in the substantia nigra with the D1 antagonist SCH-23390. The D2 agonist LY-171555 did not modulate the threshold for limbic seizures when injected into the substantia nigra. In the striatum, the D2 agonist LY-171555 protected rats against limbic seizures induced by systemic administration of pilocarpine (380 mg/kg; i.p.), with an ED50 of 2 pmol (range 1.4-2.8 pmol). The anticonvulsant action of LY-171555 in the striatum was reversed by haloperidol. The D1 agonist SKF-38393 did not affect pilocarpine seizures following administration into the striatum. Systemic administration of DAergic drugs showed that the D1 agonist SKF-38393 decreased the threshold for pilocarpine seizures, with an ED50 of 0.81 mg/kg (range 0.45-1.47 mg/kg), whereas the D2 agonist LY-171555 had no effect on susceptibility of rats to pilocarpine. The proconvulsant action of SKF-38393 was blocked by the D1 antagonist SCH-23390. These results suggest that DA differentially modulates seizure threshold in the forebrain acting via D1 mechanisms in the substantia nigra and D2 mechanisms in the striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Amygdaloid kindling and kindled seizures in rats receiving chronic ethanol administration.

The effects of chronic ethanol administration were studied in rats receiving amygdaloid kindling. Daily ethanol administration 10 min prior to kindling stimulation delayed acquisition of kindling without affecting the electrical afterdischarge. For the lowest tested dose of ethanol (0.5 g/kg), this delay was restricted to kindling stages 1 and 2. For the higher doses of ethanol (1.0 and 1.5 g/kg) this delay became more severe and stages 3 and 4 were blocked. Ethanol produced a clear dose-related anticonvulsant effect upon kindled seizures. After repeated exposure to kindling stimulation and ethanol this anticonvulsant effect vanished. After a 15-day interval without stimulation or ethanol application kindled animals were insensitive to ethanol's anticonvulsant effect. In conclusion, it is suggested that the anticonvulsant effects of low ethanol doses are restricted to kindling stages 1 and 2 and that anticonvulsant effects of high ethanol doses are limited by tolerance and by the level of consolidation of the kindled seizure. Finally, we suggest that the anticonvulsant properties of ethanol are not due to its general depressant effect but to some rather specific action.

Amygdala↗
PubMed1990

Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy.

Seizures induced by pilocarpine (PILO) have proven to be a useful procedure for investigating the basic mechanisms essential for generation, spread and motor expression of seizures in rodents. Here we report the long-term effects of PILO in rats. Following PILO (380 mg/kg, IP), 3 distinct phases were observed: 1) an acute period which lasted 1-2 days which corresponds to the pattern of repetitive seizures and status epilepticus; 2) a silent period (4-44 days) characterized by a progressive return to normal EEG and behavior; and 3) a period of recurrent seizures which started 5-45 days after PILO and lasted up to 120 days. These seizures lasted up to 50-60 sec, recurred 2-3 times per week and were more frequent during the light period of the light-dark cycle. These serial events offer a new method to induce spontaneous recurrent seizures in rats.

Aggression↗
PubMed1990

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 electrochemical 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 steps: protein precipitation with perchloric acid and pH adjustment to near 3.0. When used in combination with methanol as ion-pair in the mobile phase, sodium dodecyl sulfate effectively separated NE (6.6 min), epinephrine (EPI, 7.9 min), DA (14.3 min) and 5-HT (29.0 min) and the high methanol concentration used prevented 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 consonant with most literature data.

Animals↗
PubMed1990

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 +/- 0.5 degrees C) 20 animals were maintained either normothermic (group NT, N = 10) or hypothermic (rectal temperature of 29 +/- 0.5 degrees C, obtained within 5 min of carotid recirculation) for 5 h (group HT, N = 10). Sham-operated animals (N = 5) were kept normothermic for 5 h following the surgical procedure. 2. After a 7-day period of survival, damage to the dorsal hippocampus was determined histopathologically by cresyl-violet staining and graded on a scale of 0 to 3. The histopathological damage observed in the CA1 subfield of the hippocampus was found to be more intense in NT than in HT gerbils (P less than 0.001, Mann-Whitney U-test). 3. These 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, treatment and interpretation of experimental brain ischemia data.

Animals↗
PubMed1990

Learning impairment in chronic epileptic rats following pilocarpine-induced status epilepticus.

Male Wistar rats were subjected to pilocarpine-induced status epilepticus and allowed to recover. 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 impairment detected in some cases of symptomatic epilepsy.

Animals↗
PubMed1990

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

The effects of amygdaloid kindled seizures during pregnancy on the concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5HT) and of their respective metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5HIAA), have been studied in the cerebral cortex, brain stem and cerebellum of rat offspring at birth. The levels of DA and NE were increased and those of HVA and MHPG were 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 levels on the postnatal period, carefully planned prospective studies are needed.

Animals↗
PubMed1990

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

In the present study glutamate decarboxylase immunoreactivity (GAD-IR) was used to quantify GABAergic neurons in the hippocampus of rats exhibiting spontaneous recurrent 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.

Animals↗