Morpho-functional effects of kainic acid injection into the cat's pulvinar-lateralis posterior nucleus complex

The histological, electroencephalographic, behavioral changes as well as the changes in the intensity threshold of stimulation necessary to induce contralateral turning were studied in 16 cats, in which kainic acid (KA) was injected locally into the pulvinar-lateralis posterior nucleus complex (P-LP). In 13 cats a stainless-steel tube with two attached electrodes was implanted in P-LP, and electrodes were also implanted in the ipsilateral dorsal hippocampus, the superior colliculus and the caudate nucleus. KA was injected through the tube using a 10 microliters Hamilton syringe. In other 3 cats, KA was injected stereotaxically through the needle of the Hamilton syringe and two electrodes were implanted in these areas after withdrawal of the syringe. The intensity thresholds of stimulation required to induce turning behavior were controlled before and after KA administration in the 13 cats with an implanted tube and only after KA injections in the three cats without a tube; in these instances the current threshold of the contralateral P-LP served as control. The histological results showed a moderate KA damage of the P-LP, with destruction of neuronal soma and gliosis and additional involvement, in all the experiments, of the dorsal hippocampus; however, passage fibers were spared by the lesions. A dose-dependent epileptic effect of KA was seen, which was slight with the 3 micrograms dose and intense with 6 micrograms. The EEG recording showed a prominent and almost simultaneous epileptic involvement of the hippocampus and the P-LP after KA, with less involvement of the other implanted structures. Turning behavior induced by electrical stimulation of the P-LP was suppressed when the electrode tip was located inside the lesioned area. When the electrode tip was placed inside a slight or moderate damaged tissue, a significative increase in current threshold was found, and finally when the tip of the electrode was outside the lesioned area no change in threshold was observed. These findings do not contradict our previous hypothesis of an intrinsic cholinergic mechanism involved in the turning response evoked by P-LP electrical stimulation, although it cannot be excluded that fibers coming presumably from the superior colliculus or pretectum may contribute to the response.     

The head-eye-body turning behavior induced by electrical or cholinergic stimulation of the pulvinar-lateralis posterior nucleus complex is not dependent on the catecholaminergic system

Two experimental designs were developed in cats in order to analyze the role of the catecholaminergic system in the turning response evoked by cholinergic or electrical stimulation of the pulvinar-lateralis posterior nucleus complex (P-LP). Twenty one adult cats were employed. In one series of experiments, nine cats had a cannula implanted in one P-LP, and through it, apomorphine alone or mixed with carbachol were microinjected. The behavior was observed and the EEG was recorded. In the second experimental design, a cannula and bipolar electrodes were implanted unilaterally in the P-LP of nine cats, and a series of electrical stimulations were performed before and after 6-OHDA administration into the P-LP, and apomorphine was injected parenterally in order to induce turning behavior. Finally three cats received 16 micrograms of 6 OHDA into the P-LP, through a Hamilton syringe and no electrodes or cannula were implanted, to study the histological damage. No evidence of involvement of the catecholaminergic system was found in either of these two experimental series. These results contrast with what has been found in the nigrostriatal dopaminergic system, where an imbalance in dopamine concentration induces turning behavior. High doses (16 micrograms) of 6-OHDA induced minimal damage in the P-LP.     

Motor effects of electrical and cholinergic stimulation of the cat's dorsal hippocampus

The effect of electrical stimulation of the dorsal hippocampus was studied in 17 adult cats with implanted electrodes and those effects of carbachol and dioxolane in a group of ten adult cats with a cannula and electrodes implanted in the above cited structure. Electrical stimulation induced a contralateral head-eye-body turning response in 3 cats (17.6%), only when it was associated with afterdischarge. On the other hand the cholinergic agonists evoked contralateral head-eye-body turning in nine out of ten cats in whom the injections were administered into the hippocampus. The fact that dioxolane, an exclusive muscarinic agonist evoked this behavior and that atropine sulfate blocked this response, favours the postulation that turning is due to activation of muscarinic receptors inside the dorsal hippocampus. Comparison was done between the hippocampal group with a group similarly studied with electrodes implanted in the pulvinar-lateralis posterior nucleus complex (P-LP), and in the caudate nucleus, in which the electrical stimulation evoked contralateral head-eye-body turning response without any EEG activation.     

Effects of cortical ablations on the turning response evoked by stimulation of the pulvinar-lateralis posterior nucleus complex in the cat

The role played by the cerebral cortex on turning responses elicited by electrical stimulation of P-LP was studied in 9 chronic cats. In three animals the sensorimotor cortex was bilaterally ablated and the threshold values for inducing a turning response were determined. None of the cats showed abnormal threshold values. In six cats the cerebral cortical area known to have reciprocal anatomical connections with P-LP was unilaterally removed. Seven days after surgery, 50% of the electrodes gave no responses; 25% evoked responses with high thresholds and 25% with normal thresholds. One month after surgery the percentages were: 14, 18 and 68 respectively. Histological findings show important fiber and neuronal degeneration in P-LP. It is postulated that this area of the cerebral cortex plays, a facilitatory role on the P-LP ability to induce turning response and that the recovery of this ability can be explained by the development of P-LP denervation supersensitivity.     

Comparative study of the epileptogenic effect of kainic acid injected into the cerebral cortex, hippocampus and amygdala in adult cats chronically implanted

Intracerebral injection of kainic acid in cerebral cortex, hippocampus or amygdala in cats chronically implanted showed that: 1) Hippocampus and amygdala presented a greater sensitivity than the cerebral cortex, while hippocampus presented a greater sensitivity than the amygdala to the generation of an epileptic focus. 2) Comparison of latency, mean duration of afterdischarges, and the mean time period to obtain the peak intensity of the afterdischarge in the three cited structures, showed that mean latency of the first afterdischarge was significantly shorter in hippocampus and amygdala compared with the cerebral cortex. Moreover the mean time period to reach the peak intensity of the afterdischarge was again shorter in the subcortical structures. 3) The epileptic foci both in hippocampus and amygdala were blocked by CNQX and muscimol. 4) The behavioral changes depended on the intensity of the epileptic process. Tonic-clonic convulsions appeared only when the motor cerebral cortex was involved. Finally, 5) kainic acid injections in hippocampus and amygdala elicited an intense neuronal destruction and gliosis of these structures. We conclude that intracerebral injection of low doses of kainic acid in cats represent a good model to study focal epileptic thresholds in the CNS.     

Change in the functional significance of structures of the cat brain as a result of reorganization of its activity

A study was carried out on 8 adult cats of functional role of the frontal, parietal and occipital parts of the neocortex, and also of the dorsal hippocampus, mediodorsal thalamic nucleus and caudate nucleus head, in realization of a delayed spatial choice (DSCh) before and after compensatory reorganizations of the brain activity caused by multiple electrical stimulation of the frontal part of the cerebral cortex. Compensatory reorganization led to a change of functional significance of these structures. While before this change the frontal cortex, hippocampus and mediodorsal thalamic nucleus were critically necessary brain areas for the realization of the DSCh, after it parietal and occipital cortical areas acquired such significance. The obtained data are discussed proceeding from the principle of the integrity in the brain activity.     

Effect of electric stimulation of the dentate nucleus on focal complexes of epileptic activity in the cerebral cortex

Acute experiments on cats were made with the use of an experimental multifocal epileptic complex (MEC) which was created by local application of different concentrations of penicillin to different zones of the neocortex. At the early stages of the MEC the epileptic activity in the seizure foci increased during electrical stimulation (ES, 100-300 Hz) of the contralateral dentate nucleus. As the epileptic activity of the MEC descended up to the disappearance of some of the dependent foci, ES elicited the suppression of the epileptic discharges in the remaining foci. ES of the dentate nucleus did not affect the overall duration of MEC existence. It is inferred that the dentate nucleus belongs to the antiepileptic system of the brain.     

Kindling of the limbic structures with a shortened interstimulus interval

We investigated the possibility to produce hippocampal or amygdala kindling syndrome in rabbits which had been electrically stimulated at a fixed interval between stimuli at 5 min. Animals were prepared with chronically implanted electrodes (neocortex, hippocampus, amygdala, nucleus caudatus). The initial stimuli produced only localized effect, but repeated applications of the stimuli progressively increased the seizure activity resulting in generalized kindled convulsions after 2-4 h period. At the first stage generalized seizures were followed by long lasting refractory period, but at the end of the procedure almost all stimuli evoke major motor seizures and recurrent widely spread electrographic epileptic changes. The most noteworthy findings emerging from this study is the inhibition of postictal seizure inhibition period. This effect was independent of whether stimulated the electrode was positioned in the hippocampus or amygdala, but the hippocampal formation occupied the central position for the once and propagation of the seizure activity in all cases. When established this syndrome persisted without any attenuation for some weeks. It was concluded that this model of rapid development of kindling syndrome is useful for investigation of the nature of epilepsy and postictal seizure inhibition.     

Effects of delta sleep-inducing peptide on the intercentral integration during experimental epilepsy

In free behavior experiments on cats it has been shown, that the intraperitoneal injection of delta-sleep-inducing peptide (100 mg/kg) may change organization of the pathology integration-epileptic discharges did not spread all the structures simultaneously. The slow-waves were registered in central medium of the thalamus and nucl. caudati. The epileptic discharges were registered first in visual and auditory cortex, hippocampus. After that they were observed in the motor cortex, nucl. caudati and centrum medianum of the thalamus.     

A study of the action of anticonvulsant drugs on an experimental model of epilepsy

Repeated electrical low intensity stimulation of various regions of the brain has been shown to induce epileptic seizure activity. This experimental model of epilepsy has been used in our laboratory in rats. Male rats, anaesthetized with nembutal (20 mg/kg, i.p.) and ketalar (60 mg/kg, i.p.) were implanted stereotaxically with electrodes in the dorsal hippocampus and neocortex and received 2 hours stimulation sessions via the hippocampal electrodes (1 sec, 60 Hz, 200-800 microA) one stimulus per minute, during which electrographical and behavioral seizures were induced. The effect of anticonvulsant drugs was tested on this model: phenobarbital (40 mg/kg) reduced the quantity of epileptic electrographic activity and abolished the behavioral aspects of the seizures; diphenylhydantoin (20 mg/kg) reduced the quantity of epileptic electrographic activity, but had no effect on the behavioral component of the seizures; diazepam (6 mg/kg) only blocked the behavioral component of the seizures leaving the animal stuporous and immobile, but the electrographical component was unaffected; carbamazepine (10 mg/kg) had no effect on the electrographical epileptic seizures and reduced the behavioral aspects, but to a lesser extent than diazepam.     

Antiepileptic effects of cerebellar nucleus dentatus electrical stimulation under different conditions of brain epileptisation

It was shown in acute experiments on cats that high frequency (100-300 Hz) electrical stimulation of dentate nucleus led to the solitary epileptic foci of relatively weak intensity suppression and at the same time caused the activation of stronger focal epileptic activity. Electrical stimulation of nucleus dentatus suppressed the epileptic activity of grand mal type and increased seizures in rats with petit mal form of epileptogenesis which was formed in rats during pentylenetatiozol kindling. It was concluded that there is a relation between the antiepileptic effects of nucleus dentatus irritation and intensity as well as the form of epileptic activity induced experimentally.     

An antagonist of GABA-B receptors potentiates activity of cortical epileptic foci

Cortical epileptic foci elicited by local application of bicuculline methiodide represent a model of interictal epileptic activity with a transition into ictal phases. We studied a role of GABA-B receptors in this model using GABA-B receptor antagonist CGP35348 in adult rats with implanted cortical electrodes and cannula. CGP35348 (100 or 200 mg/kg i.p.) did not affect interictal discharges but it augmented ictal activity. Latency to the first ictal episode was decreased by the lower dose of CGP35348, duration of episodes was increased by the higher dose. GABA-B receptor antagonist did not influence purely cortical epileptic phenomenon but it is proconvulsant in ictal activity generated with participation of subcortical structures.     

Effects of activation and lesions of the superior colliculi of the lamina quadrigemina on epileptic activity in rats]

In acute experiments on rats it was shown that activation of SC by bilateral microinjection of penicillin (5-15 IU) or bicuculline (25-50 ng) resulted in the increased latency and decreased severity of i.p. picrotoxin-induced seizures (2 mg/kg). The suppression of behavioral convulsions and the decreased epileptic activity in the hippocampus and cerebral cortex were followed by occurrence of spike discharges in SC with an amplitude of 200-500 mcV and frequency of 5-12/sec which testifies to the formation of penicillin- or bicuculline-induced generator excitation in SC. The lesions of SC by kainic acid administration resulted in the decreased seizure threshold and, also, facilitated the development of seizure under conditions of picrotoxin kindling. The conclusion is made that SC activation plays an important role in the realization of functional integrative activity of the antiepileptic system.     

Unilateral epilepsy and the asymmetry of postepileptic sleep

In the paper the analysis is given of "penicillin" epilepsy in animals (cats) in conditions of different forms of deafferentation of one of the halves of the fore brain. It is shown, that in conditions of combined section of one half of the operculum of the midbrain and commissural systems of the endbrain, diencephalon and midbrain, under large doses of penicillin, unilateral convulsive activity is recorded in summate electrical activity of one of the brain halves at the side of the midbrain lesion. After the completion of unilateral organization of the epileptic process an asymmetrical sleep takes place: at the side, at which epileptiform activity was recorded, a more deep phase of the sleep appears than in the opposite brain half.     

Changes of immunoreactive somatostatin and beta-endorphin content in rat brain after amygdaloid kindling

A possible contribution of brain beta-endorphin and somatostatin to the epileptogenicity established by amygdaloid kindling was investigated in rats. Fourteen male rats were chronically implanted with electrodes placed bilaterally into the amygdala. The rats received 1 sec of electrical stimulation to the left amygdala each day. Generalized seizures were observed on average 10 days after initiation of kindling and the electrical stimulation was continued up to twenty-one days. Two months after the completion of the kindling procedure, each kindled and control rat was killed by microwave irradiation and the brains were dissected on ice into thirteen subregions. Each region was homogenized and centrifuged twice in 0.1 N acetic acid. The supernatant extracts were decanted and stored at - 20 degrees C until assay. Immunoreactive beta-endorphin and somatostatin were measured by radioimmunoassays. There were no significant differences in brain beta-endorphin contents between the two groups. In kindled rats, immunoreactive somatostatin was increased significantly in amygdala, sensorimotor, piriform, and entorhinal cortex. The results suggest that changes in somatostatin may be associated with epileptic susceptibility induced by the electrical kindling procedure.     

The typological characteristics of higher nervous activity in dogs and the maxima of the cross-correlation function between the electrical activities of the frontal cortex and the brain limbic systems]

Electrical activity of the frontal cortex, dorsal hippocampus, basolateral amygdala and lateral hypothalamus was recorded in eight dogs with chronically implanted electrodes. Mean values of the maxima of crosscorrelation function (MCCF) between electrical potentials in the theta, alpha and beta-2 ranges were used as a basis for assessment of conditions for interaction between these structures. Typological features of the higher nervous activity were assessed by the animal performance under conditions of free choice of the reinforcement mode of a conditioned stimulus: either high probable but of low alimentary quality or with low probability but more valuable. The mean MCCF values in the theta range were higher than in the other ranges. The brain structure which had the high MCCF in the theta-range, at least, with two of the structures under study was considered as "dominant". It was shown that hippocampus was the dominant structure for melancholic dogs, the frontal cortex was in phlegmatics. The hypothalamus was shown to be the "dominant structure" in both sanguine and choleric animals, but, for the most part, its activity was correlated with different structures. Thus, conditions for interaction between the frontal cortex, hippocampus, amygdala and hypothalamus seem to be an important factor, which determines typological features of the higher nervous activity of dogs.     

胃多导电刺激及胃液体排空犬动物模型的建立

目的建立胃浆膜多导联电刺激和胃排空动物模型。方法在12条英国比格犬的胃大弯浆膜层包埋四对心内起搏电极,距幽门40cm空肠近端行一造瘘口。结果①造瘘管收集食糜的方法简单易行,通过其排空量,能了解不同的电刺激和不同的电刺激参数对胃动力的作用。②胃浆膜多导联电极记录的胃体、胃窦慢波电信号清晰、稳定,能准确地记录不同时间和不同实验的胃慢波变化。③单导联和多导长脉冲电刺激均能控制胃慢波。结论胃浆膜多导联电极是研究胃电生理、胃电起搏及胃电起搏对胃排空的影响较理想的方法。英国比格犬是此模型的理想材料。     

The ACTH and cortisol content of the blood in experimental focal epilepsy

In experiments on 87 freely behaving rats and 7 cats treated with d-tubocurarine and anesthetized with nembutal it was established that the generation of focus of epileptic activity (EA) in cerebral cortex by surface application of sodium benzylpenicillin is accompanied by an increase in the plasma level of ACTH (2-fold in rats and 2.5-fold in cats) with consequent rise in the plasma cortisol level (1.5-fold both in rats and cats). In cats a "delayed" rise in plasma ACTH was observed after the cessation of cortical EA. The described changes in plasma ACTH are a result of the pathological hyperactivity of neurons rather then a stressor component under the EA.     

Anticonvulsant properties of the cerebrospinal fluid during activation of the antiepileptic system of the brain

Cerebrospinal fluid (CSF) was obtained after 30-40 sessions of daily electrical stimulation of the cat cerebellum vermis. The intraventricular injection of CSF (10 microliters) to Wistar rats increased the latent period of initial seizure manifestations, significantly reduced the number of animals with seizures and reduced the severity of seizures induced by korazol injection (40 mg/kg). Analogous seizure changes were observed in rats after intraventricular injection of CSF (10 microliters) from cats subject to 3-10 electroshock seizure fits. Intraventricular injection of CSF (250 microliters) obtained from cats after electroshock to cats with strychnine-induced epileptic foci in the brain cortex led to the suppression of the epileptic activity. The conclusion was made that different ways of antiepileptic system activation cause the accumulation of endogenous antiepileptic substances in CSF.     

Distribution of 1-14C palmitic acid in brain tissue after intraventricular injection in the conscious cat]

The distribution of (1-14C) palmitic acid in the brain tissue following the injection into the cerebral ventricles of conscious cats was investigated. The radioactive material was found in the brain tissue surrounding the cerebral ventricles and in the cerebral cortex, but in varying amounts : the smallest amounts were found in the cerebral cortex, while the highest in the thalamus and in the hippocampus. Radioactive material was also found in the peripheral venous blood. The amount of the radioactive material in the grey matter lining the cerebral ventricles as well as in the cerebral cortex was time-dependant. The labelled material in the structures surrounding the cerebral ventricles and in the cerebral cortex increased within first four hours after its intraventricular administration. Thereafter, throughout subsequent 48 hours either it slowly disappeared in the caudate nucleus and in the thalamus, or it was retained in the hypothalamus and in the floor of the IV ventricle.