Ontogeny of susceptibility to the convulsant, Ro 5-4864, and its relationship to audiogenic seizure susceptibility in inbred mice

The postnatal development of susceptibility to the convulsant effects of Ro5-4864 (4'-chlorodiazepam) was characterized in two inbred mouse strains (DBA/2J and BALB/c ByJ) which as adults differ markedly in their response to this convulsant. Onset of susceptibility to a dose of Ro5-4864 which caused a high frequency of clonic seizures in adults was observed at 10 days of age in DBA/2 mice, but not until 35 days in BALB/c By mice. At 14 days of age an abrupt increase in susceptibility to Ro5-4864-induced tonic seizures was found in DBA/2 but not BALB/c By mice. Both the peak of tonic seizure susceptibility (21 days) and the time course of its subsequent age-dependent decline closely paralleled the change in audiogenic seizure susceptibility in the DBA/2 strain. PK11195 (40 mg/kg) blocked Ro5-4864 (25 mg/kg)-induced, age-dependent tonic seizures but had no effect on clonic seizure induction in the same mice. These observations establish that both the susceptibility to Ro5-4864 in adult mice and the postnatal time course for development of susceptibility to this convulsant are inherently different in these two strains of mice. The lack of coincidence between the developmental onset of susceptibility to Ro5-4864-induced seizures and the onset of supersensitivity to Ro5-4864-induced tonic seizures during the period of peak audiogenic seizure susceptibility in DBA/2 mice implies that more than one neurochemical mechanism is involved in the ability of Ro5-4864 to induce seizures in this strain. However, the blockade of Ro5-4864-induced tonic seizures by PK11195 suggests that peripheral type benzodiazepine receptors may mediate this effect.     

Correlation between brain glycogen and convulsive state in mice submitted to methionine sulfoximine

It is now well established that in epileptic patients, hypometabolic foci appear during interictal periods. The meaning and the mechanism of such an hypometabolism are as yet unclear. The aim of the present investigation was to look for a putative relationship between glucose metabolism in the brain and the genesis of seizures in mice using administration of the convulsant, methionine sulfoximine. Besides its epileptic action, methionine sulfoximine is a powerful glycogenic agent. We analyzed the epileptogenic and glycogenic effects of methionine sulfoximine in two inbred mouse strains with different susceptibility towards the convulsant. CBA/J mice displayed high response to methionine sulfoximine. The tonic convulsions appeared 5-6 h after MSO administration, without brain glycogen content variations during the preconvulsive period. These mice died of status epilepticus during the first seizure(s). Conversely, C57BL/6J mice displayed low response to MSO. The tonic and clonic seizures appeared 8 to 14 h after MSO administration with only 2% mortality. The seizures were preceded by an increase in brain glycogen content during the preconvulsive period. Moreover, during seizures, C57BL/6J mice were able to mobilize this accumulated brain glycogen, that returned to high value after seizures. The epileptic and glycogenic responses of the parental strains were also observed in mice of the F2 generation. The F2 mice that convulsed early (16%) did not utilize their small increase in brain glycogen content, and resembled CBA/J mice; while the F2 mice that seized tardily (24%) increased their brain glycogen content before convulsion, utilized it during convulsions, and resembled C57BL/6J mice. Sixty percent of the F2 mice presented an intermediate pattern in epileptogenic responses to the convulsant. These data suggest a possible genetic link between the two MSO effects, epileptiform seizures and increase in brain glycogen content. The increase in brain glycogen content and the capability of its mobilization during seizures could delay the seizure's onset and could be considered a "resistance factor" against the seizures.     

Age related increased threshold for electroshock seizure in BDF1 mice

The thresholds for inducing the minimal and maximal electroshock seizures were examined in relation to age in BDF1 mice of both sexes. The 50 percent effective intensities for the maximal electroshock seizure (tonic hindlimb extensor component) were lowest in the youngest age groups (6-month-old) for both male (10.68 mA) and female (9.18 mA) animals. The threshold increased with age and became significantly higher at 24 months (14.00 mA, 12.70 mA for male and female mice respectively). There was also a further increase in threshold at 30 months for both sexes. Similarly, the threshold for inducing the minimal seizure also increased with age but the differences in mean threshold levels between the youngest and oldest groups were much smaller in comparison to the maximal seizure. It was concluded that the threshold for inducing electroshock seizures significantly increases with age in mice of both sexes.     

Electroconvulsive Thresholds of Inbred Mouse Strains

The electroconvulsive threshold (ECT) test is used commonly in the screening of anti-epileptic drugs in rodent models, but little is known about its genetic or mechanistic basis. Thresholds for minimal clonic, maximal tonic, or psychomotor (partial) seizures were determined in 16 different inbred mouse strains in two different laboratories. A wide range of thresholds was observed, suggesting that a variety of neuroexcitability alleles exist in inbred strains. Although there was generally good cross-strain correlation between the three seizure types, several outlier strains were detected, showing that genetically encoded differences can affect the ability of a particular seizure type to spread through the brain. Furthermore, the relative seizure susceptibility of a strain was comparable between the two laboratories, suggesting that despite different test sites, instrumentation, and personnel, the ECT assay is portable and that common inbred strains can often be relied upon as calibration standards. Last, the ECT paradigm was also sensitive enough to detect single locus differences, laying the groundwork for mutation screens for new neuroexcitability models.     

Acupuncture on experimental epilepsies

The therapeutic effect of acupuncture on epilepsies was evaluated in 4 experimental models. 24 acupuncture points were tried. In electroconvulsive threshold model, square wave electrical stimulus of 0.2 msec and 6 Hz was applied through a pair of cotton electrodes at the cornea of mice for 3 sec. The stimulus intensity to induce stun reaction of the mouse was compared. In 86 control animals, the stimulus threshold was 0.70 +/- 0.22 mA. In the acupuncture treated group (N = 80), the threshold was 0.75 +/- 0.14 mA. In maximal electroshock model, the stimulus parameters were 60 Hz, 0.4 sec and 75 mA. The tonic extensor response of the hindlimbs of the mice was observed. 75.7% of the 115 control mice and 77.5% of the 80 acupuncture treated mice were observed to have tonic extensor response. In the focal cortical penicillin model, penicillin was applied at the subpial space over the exposed cortex of 24 cats. After the appearance of repeated spikes in ECoG, acupuncture was performed. In 175 trials the interictal spikes were decreased in 16 times, increased in 82 times. In 99 trials during seizures, the ictal activity was decreased in 4 times, increased in 79 times. In the intravenous penicillin model, high dose penicillin (1,000,000-1,500,000 U/kg) was given to 20 cats. It induced repetitive spikes and frequently even seizure discharges in EEG. Acupuncture was then tried. In 192 instances, acupuncture reduced the spikes in 13, increased the spikes in 103 times. In 74 trials during seizures, the ictal activity was suppressed in 4 times and aggravated in 66 times.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study of Uridine Effect on the Development of Audiogenic Tonic Seizures in Krushinsky–Molodkina Strain Rats

The latency of tonic seizure in response to loud sound (in rats of the Krushinsky–Molodkina strain with audiogenic epilepsy) had been slightly (although statistically significantly) longer after chronic uridine injections (100 mg/kg, i.p., three times a day during 9 or 12 days). The recovery time from the tonic seizure was shorter after 12 days of injections in comparison to the 9-day injection period. At the same time, the intensity of tonic seizures provoked by loud sound did not change after chronic uridine injections. The lack of uridine anticonvulsive effect demonstrated in the audiogenic epilepsy model contradicts the anticonvulsant effects of uridine in experiments with other seizure models, in which the epileptic foci were localized in the forebrain structures.     

Role of the brain-stem reticular formation in tonic-clonic seizures: lesion and pharmacological studies

Bilateral lesions of the pontine tegmentum involving the superior cerebellar peduncles and the nucleus reticularis pontis oralis have been shown to attenuate the tonic components of maximal seizures induced by electroshock, sound stimulation (audiogenic), or pentylenetetrazol, although having no effect on clonus in three separate seizure models. The pontine tegmental lesion also abolishes the clonus of minimal audiogenic seizures that have a motor pattern different from that of other clonic models, and are believed to originate in the brain stem. The preponderant suppression of tonus by the pontine tegmental lesion as well as the inhibition of clonus in audiogenic seizures is strikingly similar to the effects of phenytoin in these same seizure models. The findings presented are consistent with the hypothesis that the pontine reticular formation (RF) plays a key role in the generation and/or expression of tonic convulsions. Additional findings are presented that suggest that serotonin may attenuate the tonic components of maximal electroshock seizures by an action on the brain stem. Thus, it seems likely that pontine tegmental lesions as well as antiepileptic drugs and neurotransmitters with preferential effects on tonic seizures act on a common neural substrate that appears to include the brain-stem RF.     

Neuropharmacological actions of panchagavya formulation containing Emblica officinalis Gaerth and Glycyrrhiza glabra Linn in mice

A panchagavya Ayurvedic formulation containing E. officinalis, G. glabra, and cow's ghee was evaluated for its effect on pentobarbital-induced sleeping time, pentylenetetrazol-induced seizures, maximal electroshock-induced seizures, spontaneous motor activity, rota-rod performance (motor coordination) and antagonism to amphetamine in mice. The formulation (300, 500 mg/kg, po) produced a significant prolongation of pentobarbital-induced sleeping time and reduced spontaneous locomotor activity. The formulation also significantly antagonised the amphetamine induced hyper-locomotor activity (500, 750 mg/kg, po) and protected mice against tonic convulsions induced by maximal electroshock (500, 750 mg/kg, po). The formulation slightly prolonged the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. The formulation did not show neurotoxicity. The results suggest that the panchagavya formulation is sedative in nature.     

The effect of audiogenic seizures on regional CNS energy reserves, glycolysis and citric acid cycle flux

Selected energy reserves, glycolytic intermediates and citric acid cycle intermediates were measured in the cerebral cortex, thalamus, brain stem, cerebellum and spinal cord of susceptible mice during audiogenic seizures. Changes in energy reserves (ATP, phosphocreatine and glucose) differed strikingly in extent and temporal pattern from region to region. The audiogenic seizure produced a transient, large decrease in thalamic energy reserves during the early, pretonic phase of the seizure. Less extensive decreases were observed in brain stem and spinal cord; but in these latter regions the changes persisted throughout the pretonic and tonic phases of the seizures. In cerebellum there was a biphasic decrease in energy reserves; a small decrease was observed immediately after the sound stimulus and a second much greater decrease was observed during the tonic phase of the seizure. No change in energy reserves was observed in cerebral cortex. Changes in glycolytic intermediates (glucose 6-phosphate, fructose diphosphate, pyruvate and lactate) also varied from region to region in response to the decreases in energy reserves. In contrast, changes in the two citric acid cycle intermediates, α-oxoglutarate and malate, were essentially the same in all regions studied. α-Oxoglutarate decreased during the tonic phase of the seizure and rose during recovery. Malate remained at control levels throughout the seizure and then slowly increased. These findings are interpreted as indicating regional variations in nueronal activity during audiogenic seizures. During the period when clinical seizure activity is apparent neuronal activity increases in the subcortical regions. This is reflected by an increase in energy utilization and an increase in glycolytic flux in these areas. However, a concomitant increase in citric acid cycle flux does not seem to occur during this period. Citric acid cycle flux does appear to increase after the seizure is over.     

Use of chromosome substitution strains to identify seizure susceptibility loci in mice

Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) × A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.     

CHANGES IN GLYCOGEN PHOSPHORYLASE ACTIVITY AND GLYCOGEN LEVELS OF MOUSE CEREBRAL CORTEX DURING CONVULSIONS INDUCED BY HOMOCYSTEINE

Glycogen phosphorylase activity and glycogen levels were investigated in the cerebral cortex of mice of two different strains under the influence of homocysteine. Control levels of glycogen and total phosphorylase activity (i. e. activity in the presence of 1 mM-AMP) were higher in the inbred strain A, whereas a higher proportion of phosphorylase in its active form (activity without 5′-AMP) was obtained in the ICR strain (probably due to slower fixation of brain in this strain). Changes occurring after the administration of homocysteine were similar in both strains. With the onset of first clonic seizures a marked increase of phosphorylase a occurred (increase 99 per cent in strain A and 46.5 per cent in ICR, respectively). During the latter phase of tonic seizures active phosphorylase a did not significantly differ from control values. Five minutes after the end of a tonic seizure, i. e. when partial recovery could already be observed, a marked decrease of active phosphorylase a in comparison with control values, was evident (decrease against control values of 45.5 per cent in strain A and 30.5 per cent in ICR, respectively). The total phosphorylase activity was not affected in strain A, whereas a slight increase during clonic seizures was seen in the ICR strain. In accordance with the enhanced activation of phosphorylase at the onset of clonic seizures, a marked decrease in glycogen levels (35-50 per cent) was observed in both strains of mice. This decrease persisted even during the 5 min recovery period. When seizures were prevented by Na phenobarbital or glycine, the activation of phosphorylase was either completely prevented (by a non-anaesthetic dose of phenobarbital) or reduced (by glycine). The present results have demonstrated that changes in glycogen metabolism occurring during homocysteine seizures differ distinctly from those previously found during seizures induced by methionine sulphoximine, a substance structurally related to homocysteine.     

Increased seizure susceptibility and cortical malformation in beta-catenin mutant mice

Beta-catenin has been implicated in epilepsy because of its altered post seizure expression and the role of Wnt2 signaling in autism. To determine beta-catenin's role in seizure susceptibility, we injected penetylenetetrazol intraperitoneally in beta-catenin cerebral cortex- and hippocampus-specific knockout mice. We then analyzed the latency, number, and duration of four phases of seizure behaviors: (I) non-seizure activity, (II) myoclonic jerks, (III) generalized clonic seizures, and (IV) tonic seizures. The latencies to both death and Phase IV were significantly reduced in mutant mice. Mutant mice also spent significantly more time in Phases III and IV and showed significantly less time in the non-convulsive state (Phase I). Nissl and gold chloride staining indicated that the knockout mice had underdeveloped cortices, lacked a corpus callosum, and were missing hippocampal structures. This suggests that dysfunction of beta-catenin-mediated signaling pathways in mice leads to cortical malformation and increased seizure susceptibility.     

Genetic and phenotypic analysis of seizure susceptibility in PL/J mice

Epilepsy is one of the most common but genetically complex neurological disorders in humans. Identifying animal models that recapitulate human epilepsies is important for pharmacological studies of anticonvulsants, dissection of molecular and biochemical pathogenesis of epilepsy, and discovery of epilepsy susceptibility genes. We discovered that the PL/J inbred mouse strain is susceptible to handling- and rhythmic tossing–induced seizure. The tonic–clonic and generalized seizures observed after induction were accompanied by abnormal EEGs, similar to seizures observed in EL and SWXL-4 mice. PL/J mice also had an extremely low threshold to electroconvulsive seizures compared to other strains and showed variable sensitivity to pentylenetetrazole-induced seizures. Gross neurostructural abnormalities were not found in PL/J mice. Crosses with the seizure-resistant C57BL/6 J strain revealed semidominant inheritance of the rhythmic tossing seizure trait with low penetrance. F2 progeny indicated that the genetic inheritance of seizure susceptibility in PL/J is non-Mendelian. We crossed DBA/2 J mice, which are resistant to rhythmic tossing seizure but susceptible to audiogenic seizures, to PL/J. We found that seizure penetrance in (DBA/2 J × PL/J)F1 mice was similar to the penetrance in (C57BL/6 J × PL/J)F1 mice but the severity and frequency of seizure were higher in (DBA/2 J × PL/J)F1 mice. The PL/J strain serves as an interesting new model for studying the genetics, neurobiology, and pharmacology of epilepsy.     

Genetic influence on increased seizure susceptibility in pregnancy

In previous studies we have reported that flurothyl-induced clonic seizure threshold was significantly reduced in pregnant mice. In the present study eight strains of mice were tested for flurothyl seizure susceptibility during pregnancy in an effort to find one which lacked this trait. Latency to myoclonus, latency to clonus, and the interval between these seizures were measured. Two inbred strains, A/Ibg and BALB/cByJ, were resistant to the pregnancy-associated increase in seizure susceptibility. These strains will be used, along with others which show the increased seizure trait, to investigate the neurochemical mechanisms which underlie the increased seizure susceptibility in pregnancy.     

Effect of drugs modifying central serotonergic function on the response of extensor and nonextensor rats to maximal electroshock

Influences of reduction or enhancement of serotonergic function on convulsive responses and thresholds to maximal electroshock stimulation (MES) were studied in rats classified by MES as extensors or nonextensors. In extensors, serotonin reduction decreased the tonic convulsive threshold coincident with an increased incidence of hindlimb extension (HLE). Enhancement of serotonergic function with fluoxetine, pCA, 5-HTP, fenfluramine or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) prevented HLE. This action was antagonized by pCA, strychnine or digitoxigenin and was not related to overt behavioral disruption or an elevated tonic threshold. In nonextensors, serotonin reduction restored HLE. HLE initiated by spinal cord stimulation was not remarkably effected by any treatment. Catecholamine reduction had no effect on any part of the tonic response in either group of rats. The results suggest the activation of central serotonergic inhibitory influences during the MES tonic convulsion. The possibility of graded-intensity serotonergic attenuation of seizure spread is discussed suggesting the action of serotonergic-enhancing drugs to prevent HLE may include a mechanism similar to a naturally-occurring “mechanism” to prevent HLE in nonextensor rats.     

The mTOR Inhibitor Rapamycin Has Limited Acute Anticonvulsant Effects in Mice

Objective

The mammalian target of rapamycin (mTOR) pathway integrates signals from different nutrient sources, including amino acids and glucose. Compounds that inhibit mTOR kinase activity such as rapamycin and everolimus can suppress seizures in some chronic animal models and in patients with tuberous sclerosis. However, it is not known whether mTOR inhibitors exert acute anticonvulsant effects in addition to their longer term antiepileptogenic effects. To gain insights into how rapamycin suppresses seizures, we investigated the anticonvulsant activity of rapamycin using acute seizure tests in mice.

Methods

Following intraperitoneal injection of rapamycin, normal four-week-old male NIH Swiss mice were evaluated for susceptibility to a battery of acute seizure tests similar to those currently used to screen potential therapeutics by the US NIH Anticonvulsant Screening Program. To assess the short term effects of rapamycin, mice were seizure tested in ≤6 hours of a single dose of rapamycin, and for longer term effects of rapamycin, mice were tested after 3 or more daily doses of rapamycin.

Results

The only seizure test where short-term rapamycin treatment protected mice was against tonic hindlimb extension in the MES threshold test, though this protection waned with longer rapamycin treatment. Longer term rapamycin treatment protected against kainic acid-induced seizure activity, but only at late times after seizure onset. Rapamycin was not protective in the 6 Hz or PTZ seizure tests after short or longer rapamycin treatment times. In contrast to other metabolism-based therapies that protect in acute seizure tests, rapamycin has limited acute anticonvulsant effects in normal mice.

Significance

The efficacy of rapamycin as an acute anticonvulsant agent may be limited. Furthermore, the combined pattern of acute seizure test results places rapamycin in a third category distinct from both fasting and the ketogenic diet, and which is more similar to drugs acting on sodium channels.     

Epilepsy and electromagnetic fields: effects of simulated atmospherics and 100-Hz magnetic fields on audiogenic seizure in rats

In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P<0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.     

Effects of iloprost, prostaglandin E1 (PGE1) and prostacyclin (PGI2) on chemically and electrically induced seizures in mice

The effects of iloprost (ZK 36,374), a new chemically stable analogue of prostacyclin (PGI2), on strychnine-, pentylene-tetrazol-, and maximal electroshock-induced seizures were studied in mice. The time from the beginning of the injection of the convulsant or inducing electroshock to the stage of persistent seizures was determined, and lack of tonic hindlimb extension was regarded as inhibition of convulsions. In doses of 8 micrograms--16 micrograms kg-1 iloprost already exhibited an anticonvulsant action by markedly reducing the incidence of seizures and mortality following strychnine, pentylenetetrazol or maximal electroshock. The onset of tonic seizures was also reduced by iloprost. PGE1 and PGI2 were generally effective in 7 to 13 times higher doses than iloprost. It is suggested that the anticonvulsant activity of iloprost, PGE1 and PGI2 might involve a common basic mechanism. Due to its efficacy, iloprost is a useful tool in the investigation of the anticonvulsant action of prostaglandins.     

Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice

Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.     

Elemental anomalies in the hippocampal formation after repetitive electrical stimulation: an X-ray fluorescence microscopy study

Our previous studies carried out on the pilocarpine model of seizures showed that highly resolved elemental analysis might be very helpful in the investigation of processes involved in the pathogenesis of epilepsy, such as excitotoxicity or mossy fiber sprouting. In this study, the changes in elemental composition that occurred in the hippocampal formation in the electrical kindling model of seizures were examined to determine the mechanisms responsible for the phenomenon of kindling and spontaneous seizure activity that may occur in this animal model. X-ray fluorescence microscopy was applied for topographic and quantitative analysis of selected elements in tissues taken from rats subjected to repetitive transauricular electroshocks (ES) and controls (N). The detailed comparisons were carried out for sectors 1 and 3 of the Ammon’s horn (CA1 and CA3, respectively), the dentate gyrus (DG) and hilus of DG. The obtained results showed only one statistically significant difference between ES and N groups, namely a higher level of Fe was noticed in CA3 region in the kindled animals. However, further analysis of correlations between the elemental levels and quantitative parameters describing electroshock-induced tonic and clonic seizures showed that the areal densities of some elements (Ca, Cu, Zn) strongly depended on the progress of kindling process. The areal density of Cu in CA1 decreased with the cumulative (totaled over 21 stimulation days) intensity and duration of electroshock-induced tonic seizures while Zn level in the hilus of DG was positively correlated with the duration and intensity of both tonic and clonic seizures.