Interrelations between the contents of transmitter amino acids in the brain structures and the level of convulsion readiness in rats

In rats with high and low levels of the audiogenic excitability (68 and 62 animals, respectivels, we measured the thresholds of convulsive reactions elicited by electrical stimulation of a few limbic and brainstem structures. The obtained figures were compared with the those of the levels of transmitter amino acids (glutamate, aspartate, glycine, and taurine) measured in the same brain structures in corresponding groups of the animals (80 rats in each group. It was found that the thresholds of convulsive reactions evoked by electrical stimulation of most tested brain structures are lower in the audiogenically excitable animals than those in the animals with high thresholds of the audiogenic excitability. These dissimilarities demonstrated certain correlation with increased glutamate concentrations in some structures under study and, probably, to a considerable extent depended on a deficiency of inhibitory amino acids, glycine and taurine, in most tested brain structures.     

Effect of seizure activity on subunit composition of Ca2+/calmodulin-dependent protein kinase II in hippocampus of Krushinskii-Molodkina rats

Using a Western blot method it was been shown that a aontent of beta-CaMKII subunit was decreased on 40 % in hippocampus of Krushinskii-Molodkina rats (rats, genetically prone to audiogenic seizures) in comparison with normal Wistar rats. Additionally, we have investigate the temporal modifications of alpha/beta-CaMKII subunits in dependent from number audiogenic fits (n = 1 or n = 5). The level of beta-CaMKII in hippocampus of naive KM rats and KM rats in 24 h after single audiogenic seizure was not different, but it was increased on 56 % through 72 h after convulsion fit. In contrast, both 5-fold seizures and 20-fold seizures (audiogenic kindling) reduced the beta-CaMKII levels in comparison with naive group. The levels of alpha-subunit protein kinase in hippocampus these experimental groups of animals were not different. We suggest a hypothesis, that modifications alpha/beta ratio can be viewed as specific "homeostatic mechanism", which provide for neuronal function in hippocampus, thereby changing the rules governing synaptic plasticity in dependence from preliminary neuronal activity.     

Effects of ionotropic glutamate receptor channel blockers on the development of audiogenic seizures in Krushinski-Molodkina rats

The action of noncompetitive blockers of glutamate receptors has been investigated on Krushinski-Molodkina rats genetically-prone to audiogenic seizures. The selective blockers of NMDA receptor channels, memantine and IEM-1921, and their dicationic homologues, IEM-1925 and IEM-1754, capable of blocking in varying degrees both NMDA and Ca-permeable AMPA receptor channels, were studied. The drugs were injected intramuscularly to rats with the different time intervals (30 min, 1, 2 or 3 hours) before sound signal. The effects of the drugs on latent period of initial locomotor activity provoked by audio stimulation (8 kHz sine-wave tone, 90 dB volume), the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. Within 30 min after injection IEM-1921 at a dose of 5 mg/kg, 33% of rats manifested a complete absence of convulsive reactions to sound, and in 59% of rats audiogenic seizures occured only in the form of motor excitation without a generalized clonic-tonic convulsions. Memantine at a dose of 5 mg/kg did not cause a complete blockade of seizures, but after 1 h of injection in 50% of the rats and after 2 h in 70% of rats a weakening of the audiogenic seizures to the level of motor excitation only was observed. After 3 hrs after administration of blockers its anticonvulsive action weakened significantly (p < 0.01). Dicationic blockers that block both NMDA and AMPA/kainate receptors, IEM-1925 (in doses of 0.001-20.0 mg/kg) and IEM-1754 (0.025-50.0 mg/kg), did not affect audiogenic clonic-tonic convulsive reactions. The involvement of activation of NMDA and calcium permeable AMPA/kainate receptors in the pathogenesis of audiogenic seizures is discussed.     

Effects of thermal preconditioning on convulsive activity in rats with inheritable form of audiogenic epilepsy

Effects of thermal preconditioning universal recognized method of increase in concentration of inducible Heat shock protein 70 kDa (Hsp70i) on characteristics of convulsive activity in Krushinskii-Molodkina (KM) rats with inheritable audiogenic epilepsy were studied. For the first time, it was found that short-term thermal preconditioning (41 degrees C during 5 minutes) increased duration of the latency of audiogenic seizure onset. Thermal preconditioning resulted in an increase in concentration of Hsp70i in amygdale, hypothalamus, midbrain; the uttermost increase was observed in hippocampus and inferior colliculus: the brain areas responsible for initiation of audiogenic seizures. A coincidence was found in the term of increase in concentration of Hsp70i and the latency of seizure onset (on day 4 after thermal preconditioning). Results of this research confirm the proposition that inducible Hsp70i is capable of taking part in the processes of seizure development in rats with inheritable form of audiogenic epilepsy.     

Electroencephalographic analysis of manifestations of latent forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of a-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. It was shown the long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of theta-diapason oscillations and with an increase of representation of alpha-diapason waves on EEG in the state of the animal quiet consciousness. A role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.     

Electroencephalographic analysis of manifestations of hidden forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of α-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. There was shown a long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of ?-diapason oscillations and with an increase of representation of α-diapason waves on EEG in the state of the animal quiet wakefulness. The role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.     

The influence of neonatal ketamine injection on pain sensitivity and audiogenic seizures in adult rats

The remote effects of neonatal (on the 3d-to-9th postnatal days) ketamine injections (10 and 50 mg/kg in 20 microliters of distilled water, s.c.) were analyzed in adult Wistar, WAG/Rij, and KM (a strain with high audiogenic sensitivity) rats. Both ketamine and water injections increased pain sensitivity in adult rats. Neonatally injected water increased the mean score of seizures in Wistar and WAG/Rij, whereas ketamine water solution injected in the dose of 50 mg/kg did not change the seizure intensity (as compared to the intact control). Consequently, ketamine significantly reduced the mean score of the audiogenic seizure fit without change in its latency. In highly sensitive KM rats the neonatally injected ketamine (50 mg/kg) significantly shortened the mean latency of the fit onset, and fit stages developed faster. Thus, the neonatal ketamine injection increased the audiogenic seizure susceptibility of brain structures in KM rats.     

3H-1-glutamate binding with the synaptic membranes isolated from the cerebral cortex and hippocampus of Krushinski?-Molodkina strain rats

Specific binding of 3H-L-glutamate to synaptic membranes isolated from the cerebral cortex and hippocamp of Wistar and Krushinsky-Molodkina (KM) rats examined both in a quiet awake state and after audiogenic seizures was compared. The dissociation constant (KD) values and binding capacity (Bmax) for KM rats did not differ significantly from the corresponding parameters of binding determined for Wistar rats (KD--89.8 +/- 18.1 and 102.6 +/- 12.5 nm, Bmax--1.23 +/- +/- 0.08 and 1.30 +/- 0.15 pmol/mg for the cortex and hippocamp, respectively). After audiogenic seizures the binding capacity of the hippocamp of KM rats was reduced by 30%. It is suggested that hippocampal glutamate receptors of KM rats are involved in the mechanism of convulsive activity formation.     

Effect of neonatal 6-hydroxydopamine treatment on audiogenic seizures

Subcutaneous injection of 6-hydroxydopamine (6-OHDA) in newborn audiogenic rats resulted in an increase in convulsive seizure intensity and a decrease in norepinephrine concentration in the cerebral cortex and the spinal cord. In addition, norepinephrine concentration in the brainstem (pons-medulla) was increased. Dopamine concentration in all brain regions studied was unchanged. The results suggest that norepinephrine exerts its modulatory influence on convulsive seizures by an action in either the spinal cord, the cerebral cortex, or both.     

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 82–88.Original Russian Text Copyright © 2005 by Vataev, Oganesyan.     

Changes of Uric Acid Level in Rat Brain After Focal Ischemia

Changes of uric acid level in rat cerebral hemisphere after left middle cerebral artery (MCA) occlusion were studied by reversed-phase HPLC with electrochemical detection. Uric acid level in the normal group was 2.98 nmol/g tissue. Uric acid concentration of the left hemisphere in the left MCA-occluded group progressively increased after occlusion, and reached a maximum value of 67.26 nmol/g tissue 24 h after ischemia. Uric acid levels in the right hemisphere remained unchanged. Uric acid concentration of the left hemisphere in sham-operated group was 9.29 nmol/g tissue 24 h after the operation.     

Are WAG/Rij rats with genetic absence epilepsy anxious?

Behavior of susceptible and non-susceptible to audiogenic (convulsive) seizures rats from inbred WAG/Rij strain, genetically predisposed to absence epilepsy, and outbred Wistar strain, genetically not predisposed to absence epilepsy, was compared to assess the level of anxiety (in open field, light-dark choice and elevated plus-maze tests) and the level of depressiveness (in the sucrose consumption and forced swimming tests). Increased level of anxiety was found only in susceptible to audiogenic seizures rats both from WAG/Rij and Wistar strain, but increased level of depressiveness was found only in WAG/Rij strain rats as compared with Wistar rats independently of their susceptibility to audiogenic seizures. Results suggest that increased depressiveness in WAG/Rij strain rats is associated with absence epilepsy but increased anxiety with susceptibility to audiogenic seizures.     

Neuronal activity in the prefrontal cortex in rats with various typological features during emotional affect

Unit activity in the right and left prefrontal cortex was recorded in male Wistar rats after testing by the emotional resonance technique. Rats were divided in two groups by their reaction to the suffering cry of a partner. Rats from the group A ("altruists") escaped partner's crying, and those from the group E ("egoists") did not. Activity of neurons was analyzed in hungry rats, after feeding, during intracranial emotionally positive and negative stimulation, and during crying of the rat partner. Some differences in neural activity between A and E groups were revealed. In the hungry state the rate of neuronal discharges was higher in the A group. In both groups of animals the positive emotional stimulation was accompanied by more intensive neuronal reaction that the negative stimulation, but in the E group increase in the rate of neuronal discharges in both hemispheres was significantly more pronounced. Negative stimulation produced in both groups a significantly greater activation in the left hemisphere than in the right one while during the positive stimulation the neural activity was more intensive in the left hemisphere. The neuronal reaction to partner's crying was significantly higher in the A group in both hemispheres, while the neuronal activity in E group did not significantly change.     

Effects of Deprivation of the Quick-Wave Sleep in Rats with Inherited Predisposition to Audiogenic Convulsions

In experiments on rats of Krushinskii–Molodkina line (KM) with genetic predisposition to audiogenic convulsions, effects of the 3- and 6-h periods of the absence of the quick-wave sleep (QS) were studied in animals under natural conditions as well as of selective deprivations of QS on EEG spectral characteristics in the wakening–sleep cycle, on organization of the cycle, and on intensity of convulsive symptoms. The QS deprivation for 3, 6, 9, and 12 h was produced by the classic methods of small platforms or of soft awakening. The data are presented about changes of the cycle parameters in the course of natural and experimental deprivations as well as about the dynamics of restoration of the cycle structure for 12 h of the post-deprivation period. It was established that during and after the QS deprivations (by any duration), in EEG of the hippocampus, caudate nucleus, medial central nucleus of thalamus, somato-sensory, visual and auditory cortex of the KM rat brain, no appearance of the paroxysmal fires was revealed in any of the states of the wakening–sleep cycle. It was also found that the selective QS deprivation did not affect duration of the latent period and parameters of the generalized tonic-clonic audiogenic convulsions. It is stated that in rats of the KM line that have the hidden convulsive syndrome, the used kinds and methods of QS deprivation fail to activate the epileptiform manifestations.     

Thermal interhemispheric asymmetry of the brain in rats in a cataleptic state]

The rat brain thermal fields were studied using the thermoencephaloscopic technique in three experimental conditions: the genetic catalepsy (GC rat strain), cataleptic phase of an audiogenic epileptic seizure (Krushinski?-Molodkina strain), and pharmacological catalepsy produced by haloperidol injection (Wistar rats). Irrespective of the experimental conditions, the state of catalepsy, accompanied by a decrease in the muscle tone and inhibition of motor reactions, was characterized by total asymmetric cooling of the brain cortex with the dominance of the right hemisphere. Temperature difference between the parieto-occipital areas of the right and left hemispheres reached 0.3-0.6 degree C.     

Asymmetry of Diacylglycerol Metabolism in Rat Cerebral Hemispheres

Diacylglycerols (DGs) were found to be asymmetrically distributed between the two cerebral hemispheres of rat brain. The left cerebral hemisphere (LCH) contained 100% more DG than the right cerebral hemisphere (RCH). The lateralization was enhanced in animals subjected to depolarization induced by a single electroconvulsive shock (ECS). During the acute phase of the convulsion, the DG pool increased in both hemispheres, with the LCH attaining a concentration 180% higher than the RCH. Stearate and arachidonate were the principal DG-acyl groups accumulated in the RCH, whereas in the LCH stearate and palmitate were mainly involved. After the last of a series of five shocks (one per day) the lateralization of the "DG response" was less accentuated during the acute phase of the ECS. Whereas DG release was drastically reduced in the LCH, in the RCH it was minimally affected. The DG sidedness after five shocks was nevertheless maintained at the level of arachidonate-containing DGs, which showed a higher accumulation in the LCH than in the RCH. The kinetics of DG removal showed a rapid phase during the first minute following a single or five ECSs. Total DG levels returned to basal values in the RCH, whereas in the LCH they remained slightly increased with respect to the initial levels 1 min after the convulsive episode. Minimal changes occurred in the subsequent 4 min. Chronic ECS altered the endogenous DG content and composition. Thus, 24 h after the last of four ECSs, total levels of DGs diminished by 40% in the RCH, whereas they remained unchanged in the LCH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interhemispheric asymmetry in the functional organization of the prefrontal cortex in animals of different typologic groups

Rats allocated to groups by the method of "emotional resonance": rats which did and did not escape crying of a partner (A- and E-groups, respectively). Unit activity in the right and left prefrontal brain cortex (PFC) was recorded in these rats. The recorded neurons neurons were divided in two groups according to their reaction to a change in the level of food motivation. The so-called D-neurons decreased their activity after feeding of animals after a 24-hour food deprivation and the other group (I-neurons) increased its firing rate rate in this situation. It was shown that hemispheric distributions of D- and I-neurons are different in selected rat groups. In E-rats the I-neurons substantially predominated in the left hemisphere, whereas the D-neurons were more frequently recorded in the right one. No such asymmetry was observed in A-group of rats. During intracranial stimulation of emotionally positive brain structures I-neurons increased their firing rate, predominantly, in the left hemisphere, whereas during intracranial emotionally negative stimulation activation of the D-neurons predominated at the right. Features of the observed functional interhemispheric asymmetry of prefrontal cortex in A- and E-groups of rats were explained by differences in the interaction between hemispheres and dissimilar activation control.     

Transcranial magnetic stimulation in research of emotion in the healthy and patients with epilepsy

The main aim of this work was by using transcranial magnetic stimulation to investigate mechanisms of interhemispheric organization the emotion in the healthy and patients with epilepsy. The research was carried out on three groups: the first and second groups of healthy and third group of the patients with idiopatical epilepsy. The first and third groups received transcranial magnetic stimulation on right and left frontalis area. The second group was control (sham transcranial magnetic stimulation). Is shown, that transcranial magnetic stimulation of right frontalis area increases the examining time on negative photos and decreases on positive photos. Transcranial magnetic stimulation of left frontalis area in the healthy and patients with epilepsy increases the examining time on positive photos and decreases on negative photos. The right hemisphere at the healthy and patients with epilepsy in the greater degree is connected to negative marks of emotions, and left hemisphere with positive marks of emotions.     

Functional asymmetry of the neocortex electrical activity during food conditioning in dogs

Four dogs were trained to perform a conditioned alimentary response to a sound stimulus. The EEG was recorded from six pairs of chronically implanted neocortical electrodes. The EEG spectra and coherence functions between the neighboring derivations of each of the hemispheres were analyzed in the theta, alpha, beta 1 and beta 2 frequency ranges. At the first stages of conditioning, the percent of cases increased when the highest mean values of EEG frequency were localized in the left hemisphere. Later on the percent of cases, when the mean coherence values in the left hemisphere were higher than in the right hemisphere, also increased. At the stage of conditioned response stabilization, this asymmetry either disappeared or the right hemisphere became more active than the left one. The spatial localization of the maximal values of the EEG frequency was different for different frequency ranges. The highest values in the beta 1 range were more frequently registered in the posterior cortical regions and in the beta 2 range they were revealed, predominantly, in the anterior areas. The maximal values of coherence dominated in the anterior regions and their spatial distribution was similar for different frequencies. Thus, the initial stages of conditioning are accompanied by activation of the left hemisphere.     

The effect of acetyldexphenmetrazine and dexphenmetrazine on the susceptibility to audiogenic seizures in mice.

The antiepileptic effect of dexphenmetrazine (DP) and acetyldexphenmetrazine (ADP) was tested on audiogenic seizures in a 100% susceptible strain of mice. DP had no antiepileptic effect, however, it markedly suppressed the postparoxysmal motor inhibition. ADP had a distinct anticonvulsive effect--it suppressed the convulsive component of the seizure, leaving its running component unaffected. The results are compared with the effect of both drugs on electrographic epileptic phenomena in the turtle brain (Servít and Strejcková 1976).