Effect of the destruction and activation of the caudate nuclei on the convulsive action of corazol kindling

Chronic experiments on the rats have shown that the pharmacological destruction of caudate nuclei significantly elevates the general brain excitation and induces rapid development of the corazol kindling. The hippocampal destruction exerts an opposite effect. Regression analysis of this processes has shown that mechanism of the general brain excitation and those of epileptogenesis are different on the stage of the developing kindling. Caudate nucleus activation induces powerful inhibition of kindling behavioral convulsive reactions and its electrographic epileptic activity. These data suggest that the caudate nucleus is a significant structure of the antiepileptic brain system and confirm G. N. Kryzhanovsky's concept about the system-antisystem interrelationship in case of neuropathologic syndromes as a result of the system hyperactivity.     

Changes in the dehydrogenase and GABA transaminase activity in the cerebral cortex during corazol kindling

The experiments on (CBA X C57BL/6)F1 mice have shown that regular corazol injections in subliminal doses stimulated seizure susceptibility (pharmacological kindling). Cytophotometric assay of the activity of oxidative metabolism enzymes (glutamate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, alpha-oxoglutarate dehydrogenase, lactate dehydrogenase) and GABA-transaminase in the sensorimotor cortex of kindled mice in post-convulsive period, and 24 hours or 30 days after corazol injections were discontinued, has revealed some specific alterations of the enzymes under study, that suggest the existence of two phases of energy metabolism disturbances. The first phase (24 hours after corazol injections were discontinued) is characterized by intensified succinic acid oxidation, while the second phase (30 days after the last injection) is characterized by anaerobic glycolysis in neuronal and glial cells. Inhibition of GABA-transaminase activity was particularly marked in postconvulsive period. From a molecular point of view these data may be considered as enzyme disturbances during stimulation of seizure susceptability or seizure activity and as a compensation component ensuring anticonvulsive mechanisms and reparative processes (antagonistic principle of molecular mechanism regulation) during activation of antiepileptic system.     

Effects of uni- and bilateral destructions of the caudate nucleus head by kainic acid on electroencephalogram in the wakefulness—sleep cycle in wistar rats

Changes in characteristics of the wakefulness—sleep cycle were studied in Wistar rats after a uni- and bilateral destruction of the head of nucleus caudatus by kainic acid that produces a selective destruction of neuronal elements but does not damage conducting pathways passing through this structure. It is established that changes of the cycle after injections of the acid did not last long (not more than 4 days) and were due to the presence of foci of paroxysmal activity resulted from a strong excitatory effect of this selective neurotoxin. It is revealed that the consequences of the bilateral injury of the nucleus caudatus were less pronounced and easier tolerated by animals than those of the unilateral one. The appearance of spindle-like discharges on rat EEG during the fast wave sleep was observed after the unilateral but not the bilateral destruction. A possible role in the genesis of this activity played by a disbalance in the work of the system of the caudate inhibitory control of the activity of non-specific thalamic nuclei is discussed.     

Effect of brain extracts from rats subjected to korazol kindling on generalized epileptic activity

The pharmacological kindling was induced in rats by corazol repeated injections in subthreshold doses. The peptide-containing fraction was emitted from animal brains by the help of hot acetic acid on the stage of generalized clonic-tonic seizures development. Intraperitoneal injection of brain extracts of kindled rats significantly increased corazol and picrotoxin induced seizure severity in mice. The effect was removed by preliminary injection of naloxone or by preventive incubation of extracts with pronase. Intraventricular injection of extracts to intact rats increased the seizure severity which was provoked by corazol and in high doses induced in rats generalized seizure reactions.     

Effects of extracts of different parts of the brain of kindled animals on seizure activity of recipient rats

The peptide-containing fraction was emitted from the hippocampal and ventral mesencephalic region tissue of rats kindled with subconvulsant doses of corazol. Extracts were prepared by the help of hot acetic acid on the stage of generalized clonic-tonic seizure development. The intraventricular injection of VMR-extracts in relatively high dose increased seizure reactions which were induced in intact recipient rats by intraperitoneal corazol injection. The intraventricular injection of the extract in relatively low dose (100 times less) suppressed corazol-induced seizures in recipients. Data are discussed from the point of view of pathological epileptic system formation and the role played by peptides in supporting it's activity during pharmacological kindling.     

Pentylenetetrazol (PTZ)-kindling development in intact and subcortical structure lesioned rats

Kindling was induced in male wistar rats (280-320 g) by daily ip injections of PTZ in subthreshold doses (30 mg/kg). Repeated administration of PTZ to animals resulted in developing of enhanced seizures and also enhanced seizure susceptibility which could be sustained for a long time (6 months) after last seizure paroxysm. The lesioned hippocampus retarded the manifestation of PTZ kindling, where as lesioned caudate nuclei increased the seizure kindling development. Results also revealed hippocampus as a determinant structure in PTZ kindling formation, which stabilize the epileptic manifestations and make them chronic, at the same time caudate nuclei retarded the epileptic seizures stabilization. This role may be only antiepileptic, and not anti-kindling as is known for caudate nuclei.     

Role of the caudate nucleus in the development of evoked synchronized activity

Synchronized activity (spindles, augmentation response) evoked by stimulation of thalamic nonspecific, association, and specific nuclei was investigated in chronic experiments on 11 cats before and after successive destruction of the caudate nuclei. After destruction of the caudate nuclei the duration of spindle activity in the frontal cortex and subcortical formations (thalamic nuclei, globus pallidus, putamen) was reduced to only three or four oscillations. In the subcortical nuclei its amplitude fell significantly (by 50±10%); in the cortex the decrease in amplitude was smaller and in some cases was not significant. Different changes were observed in the amplitude of the augmentation response, depending on where it was recorded. In the subcortical formations it was considerably and persistently reduced (by 50±10%); in the cortex these changes were unstable in character. Unilateral destruction of the caudate nucleus inhibited synchronized activity evoked by stimulation of the thalamic nuclei on the side of the operation only. Destruction of the basal ganglia (caudate nucleus, globus pallidus, entopeduncular nucleus, and putamen) did not prevent the appearance of synchronized activity; just as after isolated destruction of the caudate nucleus, after this operation synchronized activity was simply reduced in duration and amplitude. It is suggested that the caudate nucleus exerts an ipsilateral facilitatory influence on the nonspecific system of the thalamus during the development of evoked synchronized activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 239–248, May–June, 1977.     

Participation of the rat caudate nucleus in the immunostimulating effect of DAGO

The data obtained suggest that administration of the DAGO increased the number of plaque- and rosette-forming cells after immunisation with the sheep red blood cells in the sham-operated Wistar rats. Following destruction of the caudate nucleus, the DAGO administration prevented the immune activation. Bilateral destruction of the caudate nucleus resulted in a considerable inhibition of the immune response as compared with the control rats. Thereupon the caudate nucleus seems to be involved in realisation of the DAGO-induced immune activation.     

Changes of the dehydrogenase activity in the hippocampus in the korazol-induced kindling phenomenon

The activity of glutamate, succinate, malate and lactate dehydrogenases in neuronal and glial hippocampal cells during corazol kindling has been cytophotometrically assessed in the experiments on (CBA X C57BL/6)F1 mice. The kindling was induced by regular intraperitoneal corazol injections in subliminal dose of 30 mg/kg. Histochemical investigations were performed 30 min, 24 hours and 30 days after the corazol injections were discontinued. The changes in the enzymatic activity revealed suggest the biphasic nature of the disturbances in energy metabolism. During the first phase (24 hours after the last injection) the enzymatic changes do not have a noticeable influence on the predominant aerobic type of oxidation. In the second phase (30 days after the last injection) lactate dehydrogenase activity significantly increases, while the activity of other enzymes under study reduces.     

Effect of delta sleep-inducing peptide, anticonvulsant preparations and nicotinamide on generalized seizure activity

The influence of delta-sleep inducing peptide (DSIP) upon seizures induced by corazol, bicuculline, picrotoxin, strychnine, thiosemicarbazide were investigated in experiments on F1(CBA X C57 BL/6) mice. It was shown that DSIP increased the latency of first seizure manifestation which were induced by corazol, bicuculline and picrotoxin and also resulted in a suppression of seizure severity of corazol and bicuculline induced seizures. Anticonvulsant action of DSIP was evident under the condition of the mild severity seizures development. The effect of DSIP was mostly pronounced in range of its doses from 10 to 100 mcg/kg. DSIP when combined with phenobarbital, carbamazepine, diphenylhydantoin or nicotinamide enhanced the antiepileptic effects of these anticonvulsant drugs.     

Analysis of the structure of the components of the convulsive action of corazole following administration of sulazepam and its metabolites to mice]

A study was made of the interrelationship between the minimal effective doses of pseudoclonic and clonico-tonic convulsions, and also tonic extension caused by the intravenous injection of corazol to mice and the effect of anticonvulsive action of sulazepam and its metabolites (diazepam, desmethyldiazepam and oxadiazepam) on this process. It was shown that all the compounds under study increased the values of the minimal effective doses by the recorded indices of the convulsive seizure, whereas the maximum of the anticonvulsive activity was reached 15 minutes after the sulazepam and oxazepam, and 5 to 30 min after diazepam administration. There proved to be a distinct correlation between the minimal effective doses values of the recorded indices of the confulsive seizure in the control animals which also persisted after the administration of the agents under study. It is supposed that sulazepam and its metabolites increased the minimal effective doses of corazol for the recorded effects, but failed to alter the general picture of the convulsive attack and did not influence the dispersion corazol dose-effect dependence.     

Characteristics of the electrical activity in hippocampal slices in mice with Corazol kindling

It has been shown in experiments on hippocampal slices of (CBA X C57BL/6)F1 mice with corazol kindling that the threshold of the appearance of the induced seizure discharge (ISD) in the area CA1 was decreased by stimulation of Schaffer collaterals. Diazepam provoked an increase in seizure susceptibility to corazol and penicillin and reduction of the ISD. The data suggest that alterations in neuronal reactivity, which follow kindling, can be found in an individual hippocampal segment, thus making it possible to investigate this phenomenon at the synaptic and molecular levels.     

Effect of xylocaine and carbachol applied to the caudate nucleus of rats on barbiturate sleeping time

Since lesion of subcortical structures may affect the barbiturate sleeping time (bST), we decided with the present study to elucidate the role of the caudate nucleus in the determination of central sensitivity to barbiturates. Rats implanted with a cannula in the caudate nucleus of one or both sides, as well as with a jugular cannula, were utilized. Intravenous injections of sodium pentobarbital (40 mg/kg), intracerebral injections of Xylocaine (0.04 microgram), carbachol (0.2 micrograms) or artificial cerebrospinal fluid (ACF) into the caudate nucleus were performed. Both Xylocaine and carbachol, but not ACF, increased the bST regardless of the preparation used, the only exception being Xylocaine which did not alter the bST, if injected into the left caudate nucleus. The results suggest that the caudate nucleus may act as a modulator of the central sensitivity to barbiturates.     

Efferent connections of the caudate nucleus in cats

Structural and ultrastructural changes in the frontal areas of the cortex and in the region of the globus pallidus were investigated after local and extensive destruction of the caudate nucleus. It was shown by the Fink-Heimer method that after local injury to the caudate nucleus by means of electrodes implanted 2–16 months before electrolytic destruction, only a few degenerating fibers of medium and thin caliber were present. Extensive destruction of the caudate nucleus (without preimplantation of electrodes) was followed by massive degeneration of fibers of different caliber in the frontal area of the cortex. After local injury to the caudate nucleus numerous thin degenerating axons 0.5–0.6 µ in diameter and degenerating terminals were found in the region of the globus pallidus. Degenerative changes in the axo-dendritic and axo-somatic terminals followed the "dark" type of course. It is concluded that no considerable direct projections of neurons of the caudate nucleus are present in the cortex. Degenerating fibers of average caliber in frontal areas of the cortex after destruction of the caudate nucleus are evidently axons of thalamic neurons and not from cells of the damaged nucleus.A. A. Bogomol'ets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 7, No. 2, pp. 165–171, March–April, 1975.     

脚内核在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨脚内核在电针镇痛及兴奋尾壳核镇痛中的作用。脚内核微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响。与正常对照组电针或兴奋尾壳核产生的抑制作用相比有显著性差异 (P <0 .0 5 ) ;与脚内核微量注射生理盐水 7d后 ,电针可提高大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比 ,有显著性差异 (P <0 0 5 )。上述结果提示 ,脚内核在电针及兴奋尾壳核镇痛中发挥重要作用     

MPTP-induced suppression of corticofugal influences on neurons of the cat caudate nucleus

In acute experiments on cats, we demonstrated that the relative number of neurons of the caudate nucleus responding to stimulation of the motor cortex with latencies shorter than 8.0 msec significantly decreased, as compared with the control, after destruction of the nigro-striatal dopaminergic system caused by a series of injections of the neurotoxin MPTP. Within 1.5 months, the number of these cells gradually recovered. We conclude that in the norm dopamine exerts an inhibitory effect on glutamatergic cortico-striatal impulsation. We hypothesize that the blockade of transmission through cortico-striatal synaptic connections under conditions of dopamine deficiency is realized due to the toxic effect of glutamate released in excessive amounts on the corresponding receptors in the above synapses. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 287–291, July–August, 2006.     

In vivo release of transmitters in the cat basal ganglia

The release of transmitters was studied in various structures of the basal ganglia in cats implanted with several push-pull cannulas. Local depolarization enhanced Met-enkephalin release in the globus pallidus. Activation of striatonigral substance P(SP) neutrons stimulated the transmitter release from terminals. Unilateral electrical stimulation of the caudate nucleus evoked GABA release in both substantia nigrae and pallidoentopeduncular nuclei. The unilateral facilitation or interruption of nigral SP transmission modified dopamine (DA) release in the ipsilateral caudate nucleus in contrast, modifications of GABAergic or glycinergic nigral transmissions induced bilateral symmetrical effects, whereas bilateral asymmetrical changes in DA release in the two caudate nuclei were seen during the unilateral modification of nigral DA transmission. Changes in the dendritic release of DA induced changes in serotonin release both in the substantia nigra and in the ipsilateral caudate nucleus. Finally, it will be shown that acetylcholinesterase can be released from the substantia nigra and the caudate nucleus through processes dependent on nerve activity.     

Qualitative and quantitative changes in phospholipid spectra of the brain of rats with corazol-induced epilepsy

The enhancement of the sum of phospholipids in seizure period was observed during initially generalized corazol seizure in white rats' cerebral cortex. This sum fell in an hour after epileptic fit. It is noted that the maintenance of lysophosphatidylcholines and phosphatidylserines enhanced during the fit, and the maintenance of phosphatidylcholines and phosphatidylethanolamines fell either in cerebral cortex, or in cerebellum. At the same time the enhancement of the mixed fraction of sphingomyelin and phosphatidylinositide level and cardiolipins-1 in the cerebral cortex was observed. The maintenance of the latter in cerebellum fell during an hour after the attack. The quantity of cardiolipins-2 in cerebellum enhanced during the attack. It is suggested that the effect of corazol seizure leads to the enhancement of lisoforms at the expense of the intensification of disintegration of other fractions of lisoforms.     

Alterations of taurine in the brain of chronic kainic acid epilepsy model

Summary. The aim of the study was to investigate the changes of taurine in the kainic acid (KA, 10 mg/kg, s.c.) chronic model of epilepsy, six months after KA application. The KA-rats used were divided into a group of animals showing weak behavioural response to KA (WDS, rare focal convulsion; rating scale <2 up to 3 h after KA injection) and a group of strong response to KA (WDS, seizures; rating >3 up to 3 h after KA injection). The brain regions investigated were caudate nucleus, substantia nigra, septum, hippocampus, amygdala/piriform cortex, and frontal, parietal, temporal and occipital cortices. KA-rats with rating <2 developed spontaneous WDS which occurred chronically and six months after KA injection increased taurine levels were found in the hippocampus (125.4% of control). KA-rats with rating >3 developed spontaneous recurrent seizures and six months after injection increased taurine levels were found in the caudate nucleus (162.5% of control) and hippocampus (126.6% of control), while reduced taurine levels were seen in the septum (78.2% of control). In summary, increased taurine levels in the hippocampus may involve processes for membrane stabilisation, thus favouring recovery after neuronal hyperactivity. The increased taurine levels in the caudate nucleus could be involved in the modulation of spontaneous recurrent seizure activity.     

Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.