Effect of nicotinamide on epileptic activity in the cerebral cortex

The experiments on cats showed that intravenous administration of nicotinamide suppresses the epileptic activity in a solitary epileptic focus as well as in the complex of epileptic foci produced by strychnine application to various cortical zones under the influence of the most powerful focus that plays the role of a determinant. After the intravenous injection of nicotinamide (50-70 mg/kg) the complex was destabilized and broken down. The epileptic activity in the dependent foci of the complex disappeared first in the more remote from the determinant focus and then in the nearer one. The determinant focus was the last to disappear. The inhibitory effect of nicotinamide is associated with antiepileptic activity. Nicotinamide is suggested to be one of the endogenous drugs which may suppress brain hyperactivity and activate the antiepileptogenic system.     

Effect of verapamil on focal epileptic activity in the rat cerebral cortex

Experiments were carried out on 64 nonanesthetized male Wistar rats (200-220 g). Epileptic foci were induced by the application of a filter paper saturated with a solution of benzylpenicillin sodium salt (12,000 and 20,000 U/ml) to the sensorimotor cortex. It was shown that subsequent intraperitoneal administration of verapamil (5 mg/kg and 10 mg/kg) during steady focal epileptic activity (EpA) resulted in the suppression of EpA in most animals. The antiepileptic effect of verapamil was manifested in a reduced frequency and amplitude of spike discharges, decreased power of epileptic foci and less frequent appearance of seizure (ictal) discharges. The role of Ca canals of neuronal membranes in the pathogenesis of epilepsy is discussed.     

Effect of nicotinamide on focal and generalized epileptic activity in the cerebral cortex

Intraperitoneal injection of nicotinamide to rats inhibits epileptic activity induced by penicillin application in the animals' brain cortex. It has been found in experimental primary-generalized epileptic activity induced by bemegride that preliminary injection of nicotinamide increased the latency of the emergence of the first epileptic seizures. Addition of nicotinamide to synaptosomal suspension inhibited accumulation in it of the products of lipid peroxidation. Relationship between antioxidant properties of nicotinamide and its antiepileptic activity is discussed.     

Effects of magnesium and nickel ions on penicillin-induced focal epileptic activity in the cerebral cortex of rats]

In experiments on freely moving male Wistar rats on the model of penicillin-induced focal epileptic activity (EA) (the application onto the sensorimotor cortex of a filter paper soaked with benzylpenicillin sodium salt solution) it was shown that addition of MgSO4 (series 1) and NiCl2 (series 2) into the solution of penicillin significantly weakened EA. The combination of Mg2+ and Ni2+ with penicillin (series 3) produced a more significant suppression of EA as compared with separate application of the above-mentioned ions: the latency period of appearance of interictal discharges (IID) increased, the frequency and amplitude of IID decreased much more, no ictal discharges appeared in any animal, the duration of epileptic foci reduced to a much greater extent. This effect can be explained by the blockade of Ca current by the above-mentioned ions. One can suppose that the amplification of antiepileptic effects of combined action of Mg2+ and Ni2+ was due to an increase in the number of blocked voltage-dependent and NMDA-operated calcium channels.     

Effects of PN 200-110 on penicillin-induced epileptic activity in the cerebral cortex of rats]

In experiments on freely moving Wistar rats it was shown that an intraperitoneal administration of PN 200-110 in a dose of 2 mg/kg in the period of steady epileptic activity (EpA) with regular generation of ictal discharges in penicillin--induced focus resulted in suppression of EpA in most animals. Antiepileptic effect of the drug was manifested by decreasing frequency appearance of ictal discharges and shortening of the epileptic focus existence time. Intraperitoneal administration (5 mg/kg) and intraventricular injection (10 nmol) of PN 200-110 20 min before the epileptic focus formation resulted in an increased latency period of appearance interictal discharges and decreased number of ictal discharges, and shortening of the existence time of epileptic focus.     

Effect of electric stimulation of the caudate nucleus on the foci of epileptic activity in the cerebral cortex

It was shown in the acute experiments on rats that caudate nucleus is one of the main structures of brain antiepileptic system. It was noted that reduction of the influence of activating cerebral structures is a tool for abolishing the proepileptic effects which occur in some cases under conditions of electrical stimulations of neostriatum. Results of the investigation confirm G. N. Kryzhanovsky theory of a role of system-antisystem interrelations in suppression of neuropathological syndromes as a result of system hyperactivity.     

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.     

Neuronal activity of the cerebral cortex in cats with conditioned inhibition

Unit activity of the somatosensory cortex was studied in chronic experiments on cats during alimentary instrumental conditioned reflex performance and elaboration of conditioned inhibition (CI). First presentations of the CI signal at the beginning of CI formation caused, due to orienting reaction to a new stimulus, a levelling of the response of the neurones to the positive conditioned signal included into the CI complex. At the stage of consolidated CI, this depression proceeded gradually during the development of conditioned inhibition caused by consecutive presentations of the nonreinforced CI combination. Two groups of neurones were involved in the process of the CI performance: one of them being the same which was activated also in response to positive stimulation during performance of the conditioned response, and the second one being areactive to the positive conditioned stimulus but reducing the frequency of the background activity.     

Effect of diazepam on electrical activity and Na,K-ATP-ase level in a penicillin-induced epileptic focus in the rat cerebral cortex

Application of penicillin solution to the motor cortex in rats evoked the appearance of interictal discharges and epileptic seizures. After administration of diazepam in a dose of 2 mg/kg, Na,K-ATPase activity in the unpurified synaptosomes fraction of the cortex in the zone of the focus was increased by practically 100% compared with the level of activity of the enzyme in the focus without diazepam. Interictal discharges and epileptic seizures underwent different changes following intramuscular injection of diazepam. The frequency and variability of amplitude of the interictal discharges increased after administration of diazepam, whereas epileptic seizures were depressed. This effect was potentiated with an increase in the dose of diazepam. It is suggested that the opposite action of diazepam on epileptic seizures and interictal discharges may be evidence that the mechanisms lying at the basis of the development of these phenomena are different.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 4, pp. 349–357, July–August, 1980.     

Effect of insulin-induced epileptic seizures on neutral glycolipids of rabbit cerebral cortex

The neutral glycolipids of rabbit central cortex were analyzed during epileptic seizures produced by insulin or pentetrazol injection. The two agents gave similar results. A decrease of glycolipid content occurred in the cortex and in the neuronal fraction during seizures. The normal glycolipid level was restored during the recovery phase.     

Changes in the spectrum of LDH isoenzymes in foci of epileptic activity induced by penicillin in the cerebral cortex of rats

The correlation between electrophysiological changes and isozymes of LDH of the rat brain cortex was studied in seizure foci induced by application of sodium penicillin. It was discovered that activity of LDH1 was suppressed, and that of LDH5 fraction was elevated in the determinant focus, which indicates the enhanced glucose anaerobic transformation. The spectrum of LDH isozymes did not practically differ from the indicators in control animals in a homotopic region of the contralateral hemisphere prior to creation of the mirror focus. The anaerobic processes were found to be increased in the mirror focus and in the determinant one as well. Similar pattern of changes in electrophysiological and neurochemical characteristics in the determinant and dependent mirror foci attests to the formation of a pathological system out of the two epileptic foci.     

Modeling of determinant and dependent foci of epileptic activity in the rat cerebral cortex]

Foci of increased excitability were created in acute experiments on rats by means of weak strychnine solutions working at independent regimens. The hyperactive excitability focus induced by means of concentrated strychnine solutions played the role of a determinant structure. The importance of the latter is in the fact that it determines the activity character of other epileptogenic foci, enhances their convulsive activity, unites them into a single functional complex and determines the behaviour of the complex as a whole. This complex can be destroyed by depression of the determinant focus activity. Switching off any dependent foci included into this complex fails to destroy that latter. Results of the investigations confirmed on the new model the general concept of the role played by the determinant structures in the brain activity.     

Effects of delta sleep-inducing peptide on electrophysiological parameters of sleep during alcohol withdrawal in rats

In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.     

Monosialoganglioside increases catalase activity in cerebral cortex of rats

Monosialoganglioside (GM1) is a neuroprotective agent that has been reported to scavenge free radicals generated during reperfusion and to protect receptors and enzymes from oxidative damage. However, only a few studies have attempted to investigate the effects of GM1 on enzymatic antioxidant defenses of the brain. In the present study, we evaluate the effects of the systemic administration of GM1 on the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and on spontaneous chemiluminescence and total radical-trapping potential (TRAP) in cerebral cortex of rats ex vivo. The effects of GM1 on CAT activity and spontaneous chemiluminescence in vitro were also determined.

Animals received two injections of GM1 (50 mg/kg, i.p.) or saline (0.85% NaCl, i.p.) spaced 24 h apart. Thirty minutes after the second injection the animals were sacrificed and enzyme activities and spontaneous chemiluminescence and TRAP were measured in cell-free homogenates. GM1 administration reduced spontaneous chemiluminescence and increased catalase activity ex vivo, but had no effect on TRAP, SOD or GSH-Px activities. GM1, at high concentrations, reduced CAT activity in vitro. We suggest that the antioxidant activity of GM1 ganglioside in the cerebral cortex may be due to an increased catalase activity.     

Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

Abstact

Background

Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue.

Methods

In the present study, alterations of the general GABA, GABA_A and GABA_B receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated.

Results

Scatchard analysis of [³H]GABA, [³H]bicuculline and [³H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in B_max (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABA_Aά1, GABA_Aγ, GABA_Aδ, GABA_B and GAD where down regulated (P < 0.001) in epileptic rats. GABA_Aά5 subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance.

Conclusions

Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.     

Afferent connections of the prefrontal cerebral cortex in cats

In experiments with unilateral injections of horseradish peroxidase microdoses into the dorsal sites of external g. proreus. using the method of retrograde axonal transport, labeled neurons have been revealed ipsilaterally in the singular cortex of telencephalon, in amygdala and thalamic structures of the brain (n.medio-dorsal nucleus, anterior group of nuclei and intralaminar nuclei). The role of the direct projections discovered to the prefrontal cortex in the formation of emotional component of pain is discussed.