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Biomedical subjects

E A Cavalheiro

Publications and source records attributed to E A Cavalheiro.

At least 91 records · Page 5Linked to original sources
PubMed1990

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

Male Wistar rats were subjected to daily sessions of electrical amygdala kindling until a generalized seizure was observed on five consecutive days. Bilateral microinjections (0.5 microliter) of ethosuximide (ETX) (10 pg/microliters) or saline were then administered through 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 amygdala-kindled seizures.

Amygdala↗
PubMed1990

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 microliters of suspension was deposited at the rate of 1 microliter/min. Control animals were not submitted to surgery (4 rats). After six weeks a marked reduction of suppression of spontaneous seizures was observed in intrahippocampally grafted rats. From these preliminary results we suggest that grafts can be used to suppress spontaneous recurrent epileptic seizures.

Adrenergic Fibers↗
PubMed1989

Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy.

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.

Animals↗
PubMed1989

Behavioural, electroencephalographic and neuropathological effects of the intrahippocampal injection of the venom of the South American rattlesnake (Crotalus durissus terrificus).

Venom was microinjected into the dorsal hippocampus of rats and electroencephalographic recordings were obtained from the hippocampus and occipital cortex. Behavioural alterations consisted of circling, wet shaking and scratching that evolved to head and body jerks and isolated clonic episodes and then to wild running followed by tonic-clonic generalized seizures and status epilepticus. Electroencephalographic alterations consisted of high frequency and high voltage spikes together with epileptiform seizures beginning in the hippocampus and evolving to the cortex. However there was only a poor electrographic-behavioural correlation between the generalized tonic-clonic seizures preceded by wild running and the electrical recordings from hippocampus and occipital cortex. Histology revealed lesions at the site of injection as well as at distant sites. Severity of neuronal damage was associated with seizure intensity. Damaged areas were almost the same as found within other models of epilepsy. Nevertheless a remarkable difference was the highly lesioned hypothalamus seen in this experiment. We discuss our results in relation to results obtained with other methods of inducing epilepsy. This venom may be a useful tool for studying the nervous system.

Animals↗
PubMed1989

The basal ganglia, the deep prepyriform cortex, and seizure spread: bicuculline is anticonvulsant in the rat striatum.

The gamma-aminobutyric acid antagonist, bicuculline methiodide (BMI), induces myoclonic seizures in rats when injected into the deep prepyriform cortex at concentrations lower than those that induce convulsions from the amygdala, hippocampus, or neocortex. This observation prompted the suggestion that the deep prepyriform cortex was responsible for seizure generation regardless of the neurotransmitter and neuronal circuits involved. Bilateral intrastriatal application of BMI protects rats against seizures induced by (i) local application of BMI into the deep prepyriform cortex and (ii) systemic application of bicuculline, pilocarpine (a cholinergic agonist), or kainic acid (a glutamate receptor agonist). The region of the striatum sensitive to the previously unknown anticonvulsant action of BMI is located in the immediate vicinity of the deep prepyriform cortex and is 100-150 times more sensitive to the anticonvulsant action relative to the sensitivity of the deep prepyriform cortex to the convulsant action of BMI. These data suggest a powerful gamma-aminobutyric acid-dependent gating role of the basal ganglia in determining the seizure threshold in the forebrain. This argues against the suggestion that the deep prepyriform cortex plays a crucial role in the generation of seizures following systemic administration of convulsants. The discovery of an anticonvulsant action of BMI in the rat striatum contradicts the gamma-aminobutyric acid theory of epilepsy, which implies that deficits in the gamma-aminobutyric acid-mediated inhibition in the central nervous system lead to the emergence of seizures.

Animals↗
PubMed1989

Convulxin does not induce convulsions when injected into the rat dorsal hippocampus.

The search for new and selective neurotoxins has attracted several efforts in the recent years. Convulxin, a neurotoxin isolated from the Crotalus durissus terrificus venom, was reported to elicit convulsions upon intravenous injection in mice and cats. Therefore we have studied the behavioral, electroencephalographic and neuropathological effects of convulxin when microinjected into the dorsal hippocampus of rats. To test the hypothesis that substances released by convulxin from platelets and not convulxin itself is the convulsive agent, we injected a mixture of convulxin and platelet rich plasma. Results demonstrated that neither convulxin nor convulxin/platelet rich plasma exhibited neurotoxic effects upon intrahippocampal injection.

Animals↗
PubMed1989

The renal effects of kainic acid.

The effect of kainic acid (KA), a potent neurotoxic agent, on the renal function of rats was investigated. Intrahippocampal and intraperitoneal KA injections (2.5 micrograms and 8 mg/kg, respectively) led to a decrease in glomerular filtration rate and U/P inulin ratio with a concomitant increase in the amount of excreted Na+. However, acid excretion was maintained. These findings support the idea of a straight connection between neurohormonal secretion and renal function and may provide an interesting model to study renal hemodynamic changes induced by neurological disturbances.

Acidosis↗
PubMed1989

Correlation of postural and pathological findings in a modified four-vessel occlusion model of rat forebrain ischemia.

1. The Pulsinelli preparation has largely simplified and avoided the complications of other models of brain ischemia in the rat. We present here modifications which improve the Pulsinelli preparation, based on a new and atraumatic technique for arterial clamping. Effective cauterization of vertebral arteries was obtained using a modified pyrographic device. Histopathological results demonstrate that the modified method was capable of reproducing the features of transient forebrain ischemia reported in the literature. 2. Consistent postural changes were induced by the ischemic insult. The intensity and interhemispheric symmetry of brain damage correlated well with the occurrence and maintenance of postural alterations throughout the ischemic period as well as with the duration of the latter.

Animals↗
PubMed1989

Characterization of convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea in rats.

To characterize the convulsions induced by a hexanic extract of Spilanthes acmella var. oleracea, male Wistar rats were injected ip with 50 to 150 mg/kg of the extract and EEG and behavior were observed for periods as long as 2 h. Following the lower doses (50 and 75 mg/kg) only minor behavioral changes such as grooming and wet dog shakes were observed. Higher doses (100 to 150 mg/kg) induced full tonic-clonic convulsions in a dose-dependent manner which were accompanied by typical electrographic seizures in the EEG. These results confirm that the hexane extract of Spilanthes acmella var. oleracea is able to induce generalized convulsions in rats and can be used as a tool in the development of new models of epilepsy.

Animals↗
PubMed1988

Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.

The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg/kg (60-174), and phenylbutazone, 59 mg/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg/kg, to a convulsant one. Indomethacin, 1-10 mg/kg, and ibuprofen, 10-100 mg/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures.

Animals↗
PubMed1988

Brain indoleamines in alloxan- and streptozotocin-induced diabetic rats.

Previous work by other authors has shown that alloxan-induced diabetes increases whereas streptozotocin-induced diabetes does not alter nonesterified fatty acid (NEFA) plasma levels. The present study replicates these results and demonstrates that fasted, streptozotocin-induced diabetic animals also have increased NEFA levels. In addition, brain levels of 5-hydroxytryptamine (5-HT) and of its immediate precursor and metabolite were measured. Alloxan- and fasted, streptozotocin-induced diabetic rats showed significant increases in brain indoleamine concentrations, whereas fed, streptozotocin-induced diabetic rats had unchanged levels of the same compounds. Levels of brain indoleamines exhibited a strong positive correlation with wet-dog shakes (an index of 5-HT activity) elicited by hippocampal stimulation. Blockade of wet-dog shakes by 5-HT receptor antagonists strengthens the proposal that this behavior is a good index of central 5-HT activity. The increased content of brain indoleamines in alloxan- and fasted, streptozotocin-induced diabetic rats may be related to the increased NEFA plasma levels seen in the same animals. This hypothesis is supported by the positive correlation demonstrated between NEFA and 5-HT levels. In conclusion, it is suggested that alloxan-induced diabetes may represent a useful model for studying the various behavioral changes known to occur in diabetics.

Alloxan↗
PubMed1988

Dopamine-sensitive anticonvulsant site in the rat striatum.

The basal ganglia are involved in the organization of movement and function in the initiation and expression of generalized and limbic seizures. Dopamine is the principal neurotransmitter of the mesencephalic efferent pathways terminating in the mammalian striatum. No function has been ascribed to mesostriatal dopamine in the control of seizure spread in the brain. This work presents evidence that bilateral application of picomole amounts of apomorphine (a dopamine agonist) into the striatum confers protection against seizures produced by pilocarpine (a cholinergic agonist) in rats. The anticonvulsant effect of apomorphine is topographically confined to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Bilateral application of nanomolar amounts of haloperidol (a dopamine antagonist) into the caudate-putamen or systemic application of haloperidol both lower the threshold for pilocarpine-induced seizures. Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine. These results suggest that dopaminergic transmission in the striatum may be operative in complex neuronal networks modulating the seizure threshold.

Amino Acids↗
PubMed1987

The susceptibility of rats to pilocarpine-induced seizures is age-dependent.

Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydrochloride were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral patterns in developing rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoclonic movements of the limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense behavioral signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12-day-old-rats. The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocampus and cortex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings during the second week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pilocarpine, 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered in 15-21-day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to motor limbic seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased susceptibility to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs, and an increased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced convulsions high voltage fast activity superposed over hippocampal theta-rhythm, progressed into high voltage spiking and spread to cortical records. The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morphological analysis of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage or an attenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological breakdown was seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in the substantia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was present in 4-5-week-old rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1987

Microinjections of the gamma-aminobutyrate antagonist, bicuculline methiodide, into the caudate-putamen prevent amygdala-kindled seizures in rats.

We used amygdala-kindled seizures in rats to study the function of striatal gamma-aminobutyrate (GABA) in the regulation of the seizure threshold of the limbic forebrain. Microinjections of the GABAA antagonist, bicuculline methiodide, 1 pmol, into the caudate-putamen protected rats against amygdala-kindled seizures. This result shows that striatal GABA differentially modulates the threshold for limbic seizures.

Amygdala↗
PubMed1987

Only certain antiepileptic drugs prevent seizures induced by pilocarpine.

Seizures produced in rats by systemically administered pilocarpine (PILO) provide a model for studying the generation and spread of convulsive activity in the forebrain. PILO, 380 mg/kg, induces a sequence of behavioral and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures in humans. The present study was undertaken to determine whether clinically utilized antiepileptic drugs share an ability to suppress seizures and brain damage elicited by PILO in rats. Clonazepam, ED50 0.35 mg/kg (0.25-0.49), phenobarbital, 23.4 mg/kg (18.5-29.6), and valproic acid, 286 mg/kg (202-405), prevented the buildup of limbic seizures and protected against seizure-related brain damage. Pretreatment with trimethadione, 179 mg/kg (116-277), resulted in a moderate protection against PILO-induced seizures, whereas carbamazepine, 10-50 mg/kg, and diphenylhydantoin, 10-200 mg/kg, blocked neither convulsions nor brain damage produced by the drug. Surprisingly, ethosuximide, 196 mg/kg (141-272), and acetazolamide, 505 mg/kg (332-766), both lowered the threshold for seizures induced by PILO and converted a non-convulsant dose of PILO, 200 mg/kg, into a convulsant one. These results indicate that only certain anticonvulsant drugs elevate the threshold for PILO-induced seizures and prevent the occurrence of epilepsy-related brain damage. The resistance of seizures produced by PILO in rats to antiepileptic drugs reaffirms the clinically obvious lack of effective treatments for limbic convulsions.

Animals↗
PubMed1987

Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae.

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗