The contribution of diffusion to the termination of penicillin-induced convulsive activity in the awake rat.

1. Experiments were performed to investigate the contribution of diffusion to the termination of PCN induced convulsive (epileptiform) activity in the awake rat. The basic question was whether convulsive activity terminates at the same critical concentration Ct of PCN independently of the concentration Co of PCN injected into the superficial layer of the foreleg field of the right motor cortex. Different concentrations Co were used, the lowest being 16 IU PCN/0.5 microliters saline, the largest 1000 IU PCN/0.5 microliters saline. The convulsive activity was recorded by means of the electroencephalogram (EEG). 2. Mathematical calculations concerning the diffusion of the substances were performed by using the diffusion equation with a PCN diffusion coefficient D = 3.52 x 10(-4) mm2/s and the tortuosity factor lambda = 1.62. 3. The lowest dose of PCN used was considered as a threshold dose for acute induction of convulsive activity because only 4 out of 9 rats treated with 16 IU PCN developed epileptiform activity. For the range of doses between 16 and 32 IU, the median frequency of convulsive potentials was dose-dependent, and increased from 7.9 to 13.8 pot./min, respectively. For higher doses covering the range between 63 and 1000 IU, there was only an insignificant increase from 19.2 to 22.7 pot./min, respectively. 4. The median period of convulsive activity increased significantly (p less than 0.05 or less than 0.01) and monotonically from 19.5 min in rats treated with 16 IU PCN to 267 min after treatment with 1000 IU PCN. 5. At the end of the convulsive activity, the median critical concentration Ct within the artificial focus ranged from 1.75 to 1.31 IU/0.5 microliters saline in rats treated with 16 to 125 IU PCN, while after induction of convulsive activity with doses of 250, 500 or 1000 IU PCN, Ct gradually increased to 2.01, 2.83, and 3.75 IU/0.5 microliters, respectively. This means that the brain became less sensitive for PCN the longer the epileptiform activity lasted. 6. It is concluded that during long-lasting convulsive activity, the brain takes advantage of its plastic properties by eliciting counteracting mechanisms. These self-protective factors may utilize neuronal networks which needs some time to become effective in the control of the cortical activity.     

颅内电极在感觉运动区皮质发育不良癫痫手术中的应用

目的：探讨长程颅内电极监测及电刺激方法,在感觉运动区皮质发育不良的难治性癫痫外科手术评估中的意义。方法：筛选MRI提示的皮质发育不良区域与重要功能区-感觉运动区位置关系密切的11例难治性癫痫患者,且头皮长程视频脑电监测及PET检查也初步提示癫痫发作与皮质发育不良所在脑区有关,在可疑脑区放置颅内电极,然后进行颅内电极长程视频脑电监测及电刺激检测,对癫痫起源位置及功能区定位,明确癫痫发作起源区域与感觉运动功能区的解剖学关系,在定位结果指导下进行切除术。结果：11例中3例位于左侧半球,8例位于右侧半球,11例感觉运动功能区皮质分布均存在不同程度变异,7例癫痫发作起源区域与感觉运动功能区一定范围重叠,其中5例与感觉区重叠,该5例切除了起源区域与发作有关的部分感觉区,2例部分致痫灶与运动区重叠,该2例仅切除了除与发作有关的运动区以外的癫痫起源区域,4例癫痫发作起源区域与感觉运动功能区相对独立,该4例完全切除癫痫发作起源区域;手术后6例患者发作消失,2例患者发作频率减少90%以上,1例癫痫发作控制无效,2例患者发生部分感觉缺失,但对生活无明显影响。结论：在皮质发育不良的癫痫患者中,有较高比例的病人伴有功能区皮层分布的变异,长程颅内电极监测及电刺激能够实现癫痫起源区域及功能区精确定位,明确功能区变异情况,对于指导病灶切除,避免损伤功能区皮质,减少术后并发症具有重要意义。     

颅内电极在感觉运动区皮质发育不良癫痫手术中的应用

目的:探讨长程颅内电极监测及电刺激方法,在感觉运动区皮质发育不良的难治性癫痫外科手术评估中的意义。方法:筛选MRI提示的皮质发育不良区域与重要功能区-感觉运动区位置关系密切的11例难治性癫痫患者,且头皮长程视频脑电监测及PET检查也初步提示癫痫发作与皮质发育不良所在脑区有关,在可疑脑区放置颅内电极,然后进行颅内电极长程视频脑电监测及电刺激检测,对癫痫起源位置及功能区定位,明确癫痫发作起源区域与感觉运动功能区的解剖学关系,在定位结果指导下进行切除术。结果:11例中3例位于左侧半球,8例位于右侧半球,11例感觉运动功能区皮质分布均存在不同程度变异,7例癫痫发作起源区域与感觉运动功能区一定范围重叠,其中5例与感觉区重叠,该5例切除了起源区域与发作有关的部分感觉区,2例部分致痫灶与运动区重叠,该2例仅切除了除与发作有关的运动区以外的癫痫起源区域,4例癫痫发作起源区域与感觉运动功能区相对独立,该4例完全切除癫痫发作起源区域;手术后6例患者发作消失,2例患者发作频率减少90%以上,1例癫痫发作控制无效,2例患者发生部分感觉缺失,但对生活无明显影响。结论:在皮质发育不良的癫痫患者中,有较高比例的病人伴有功能区皮层分布的变异,长程颅内电极监测及电刺激能够实现癫痫起源区域及功能区精确定位,明确功能区变异情况,对于指导病灶切除,避免损伤功能区皮质,减少术后并发症具有重要意义。     

Spontaneous and evoked activities of interpositus nucleus neurons before and after lesion of the cerebellar cortex

Spontaneous and evoked activities of nucleus interpositus neurons (IN) of the cerebellum were examined before and after cerebellar paravermal cortex lesions in cats anesthetized with alpha-chloralose. It was found that spontaneous activity increased dramatically following cortical ablation: before the lesion only 4% of cells encountered fired at a rate exceeding 80 impulses/sec., whereas up to 40% discharged at this rate postoperatively. Responses to paw stimulation were also altered: the initial excitation was lengthened from 8.5 to 15.8 msec; narrow; trough causing segmentation in this excitation, which seems to result from Purkinje cell inhibition, was absent; and the succeeding inhibitory period was reduced in duration by 50%. Also after the lesion there was a strong tendency for the neurons to discharge in bursts. It is suggested that changes in cell activity in the IN following cortical lesion unveil neural mechanisms of motor disturbances in lesioned cats.     

Spectral and coherence EEG analysis of rats differing in the level of seizure readiness

The resting EEGs of several brain structures (motor and visual cortex, caudate nucleus and intralaminar thalamic nuclei) were submitted to spectral and coherence computer analyses in two rat strains. Genetically predisposed to convulsive state KM rats were shown to differ from nonpredisposed Wistar rats in EEG spectral properties. KM rats EEG pattern was characterized by increase of low frequencies (1-2 Hz) power and decrease of faster activity (5-12 Hz) power in cortical spectrograms as well as by decrease of caudate nucleus EEG absolute power. The coherence value between cortical or subcortical structures at below 4 Hz was intensified in KM rats. Reinforcement of cortical auto-oscillating properties manifested by ECoG synchronization in cortical-thalamic resonance interaction as well as weakening of striatal inhibitory system may constitute neurophysiological mechanisms of enhanced convulsive readiness. The probable role of mediator imbalance in these mechanisms is discussed.     

Long-term action of camphor on "audio-sensitive" rats: Electrophysiological study and mathematical modeling of properties of neuronal networks

Krushinskii-Molodkina (KM) strain rats genetically predisposed to audiogenic convulsive reaction were given repeated camphor injections in gradually increasing doses (starting at the minimum threshold level required for seizures to occur) over a 4–5 month period. Animals were able to tolerate camphor at doses 3/2–3 times convulsion threshold level without seizure occurring once habituation to the action of this convulsant had been developed. At the same time, the cortical motor zone of strain KM rats acquired properties typical of an epileptic focus: spontaneous epileptiform firing peaks were noted in the background electrical activity of this zone. A decline in the parameter reflecting efficacy of the mechanisms underlying recurrent inhibition emerged in the cortical motor zone of strain KM rats receiving camphor from calculating the parameters of neuronal network from spectra of summated potentials (using the model of a neuronal network). It is suggested that the development of compensatory processes making it possible to avoid generalized seizure following administration of camphor in large doses is associated with intensification of inhibitory caudate function and attenuated hippocampal excitation.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 193–200, March–April, 1990.     

A morphofunctional analysis of the participation of the cerebral cortex in the habituation of Krushinski?-Molodkina strain rats to an epileptogenic stimulus

Systematic action of epileptogenic stimulus (sound) leads to gradual lowering of the level of convulsive readiness (LCR) in rats of KM (Krushinski'i-Molodkina) line to the formation of the habituation, to blocking of convulsive seizures. It is shown that at single action of sound, functional switching-off of the cerebral cortex causes LCR lowering but does not prevent the development of the epileptiform seizure. Alongside with it, in conditions of repeated sound action, functional decortication considerably retards LCR lowering. After cessation of the cortical depression, during which the rats were given systematic sound exposition, sharp LCR lowering takes place. If the habituation has been already formed, then the subsequent switching-off of the cortex does not lead to LCR growth. Ultrastructural characteristics of asymmetric axo-dendritic and axo-spine synapses in the auditory cerebral cortex of KM line rats in the moment of convulsive seizure testifies to their active functioning, while against the background of short-term habituation to epileptogenic stimulus signs of lowering of the efficiency of synaptic transmission are revealed in these synapses. The obtained results allow to suggest that in the rats of KM line the neocortex takes part in antiepileptic defensive reactions, in LCR regulation in connection with formation of the habituation to systematic action of epileptogenic stimulus.     

Effect of inferior olive lesion on seizure threshold in the rat

Cerebellar stimulation has been associated with anticonvulsant activity in several experimental seizure models. We examined the effect of destruction of cerebellar climbing fibers, by systemic administration of 3-acetylpyridine (3AP) or electrothermic lesion of the inferior olive, on seizures produced by various chemical convulsants in rats. We found that inferior olive lesioned rats had lower threshold to seizures induced by strychnine and brucine, both glycine antagonists. The dose response curve for strychnine seizure was shifted 2.5 times to the left in 3AP lesioned rats. No difference in seizure threshold was seen when picrotoxin, bicuculline or pentylenetetrazole PTZ) were used to produce seizures. Abnormal motor behavior (AMB) including myoclonus, backward movement and hyperextension, produced by all of the convulsants tested, was significantly aggravated in 3AP pretreated rats. The inferior olive-climbing fiber projection to the cerebellum appears to modulate seizures induced by inhibition of glycinergic neurotransmission.     

Effect of a Ca-channel blocker, ryodipine, on focal and generalized epileptic activity

The experiments were performed on 102 freely moving Wistar rats. Epileptic foci were produced by the application of a filter paper soaked in a sodium benzylpenicillin solution (20,000 IU/ml) onto sensorimotor cortex. It was shown that an intraperitoneal administration of ryodipine (1,2 and 5 mg/kg) during a steady epileptic activity (EA) resulted in suppression of EA in most animals. Antiepileptic effect of ryodipine was manifested by a decreased frequency and amplitude of interictal discharges and a less frequent appearance of ictal discharges (ID). Prior administration of ryodipine (2 mg/kg) 30 min before producing the focus of EA resulted in an increased latency and decreased number of ID, and shortening of the duration of the focus of EA. Generalized convulsions were induced by intraperitoneal of pentylenetetrazol (60 mg/kg). Ryodipine (2 mg/kg, 30 min before pentylenetetrazol) increased latency to first convulsive episodes and delayed the development of generalized tonic-clonic seizures.     

The role of the pallidum in regulating cortical activity]

Bilateral ablation of the pallidum halves the duration of extinction of conditioned motor food reflexes and contributes to 30 to 50% extinction of the electro-defensive reflexes. Pallidum functional depression by potassium chloride or novacaine leads to a temporary total depression of conditioned motor food reflexes. Depending on the frequency of pallidum stimulation, synchronization or desynchronization of the cortical bioelectrical activity is observed. Ablation of the pallidum in anaesthetized cats results in a high amplitude and low-frequency cortical activity. Injection of large doses of potassium chloride into the pallidum results in a forced running forward which lasts 30 to 40 min. The pallidum is considreed as a structure controlling the cortex activity, which takes part in the mechanisms of sensory information processes in the course of adaptive behaviour.     

Synthesis of Serotonin in Traumatized Rat Brain

Abstract: Previous studies have demonstrated that focal freezing lesions in rats cause a widespread decrease of cortical glucose use in the lesioned hemisphere and this was interpreted as a reflection of depression of cortical activity. The serotonergic neurotransmitter system was implicated in these alterations when it was shown that (1) cortical serotonin metabolism was increased widely in focally injured brain and (2) inhibition of serotonin synthesis prevented the development of cortical hypometabolism. In the present studies we applied an autoradiographic method that uses the accumulation of the ¹⁴C-labeled analogue of serotonin α-methylserotonin to assess changes in the rate of serotonin synthesis in injured brain. The results confirmed that 3 days after the lesion was made, at the time of greatest depression of glucose use, serotonin synthesis was significantly increased in cortical areas throughout the injured hemisphere. The increase was also seen in the dorsal hippocampus and area CA3, as well as in the medial geniculate and dorsal raphe, but not in any other subcortical structures including median raphe. Present results suggest that the functional changes in the cortex of the lesioned hemisphere are associated with an increased rate of serotonin synthesis mediated by activation of the dorsal raphe. We also documented by α-[¹⁴C]aminoisobutyric acid autoradiography that there was increased permeability of the blood-brain barrier, but this was restricted to the rim of the lesion.     

Effect of chronic para-chlorophenylalanine treatment on convulsive-seizure reactions

The effect of chronic para-chlorphenylalanine (PCPA) treatment was investigated in two different seizure models: the pentylenetetrazole (PTX) seizure model in rats and the kindled seizures from rabbit amygdala. Chronic PCPA treatment (21 days) in male albino rats caused a progressive decrease in the 5-hydroxytryptamine (5-HT) brain level between the 1st and the 7th day of PCPA administration. Then the 5-HT level remained low until the end of the experiment. On the background of the low 5-HT level there occurred changes in PTZ convulsive reactions: after the 3rd day of PCPA treatment the convulsive-seizure reactivity was significantly increased and after the 7th, 14th and 21st day the increased seizure reactivity performed only as a tendency, though the 5-HT level was still low. Chronic PCPA treatment (16 days) of rabbits delayed the development of the behavioural kindled seizures. This treatment also reduced the duration of bioelectrical seizures until the 8th day of treatment, especially in the motor cortex. The observed different effect of the chronic PCPA treatment in both seizure models: pentylenetetrazole in rats and kindling in rabbits might be explained by essential differences in the origin and mechanisms of development of the two seizure models.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4γ, 4δ, 6aα, 6aγ, 3a. The lesions were mainly in area 4γ. In the lesioned hemisphere there were many points around the lesion site (in areas 4γ and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6aγ) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4γ, 6aγ and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.     

Grafting of genetically modified cells: effects of acetylcholine release in vivo.

In this study, microdialysis was used to investigate functional recovery of central cholinergic neurons in the forebrain of rats with cortical devascularizing lesions. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and genetically modified fibroblasts secreting nerve growth factor (NGF) were placed at the site of the lesion. One month following surgery, microdialysis probes were installed in the remaining cortex and were perfused with artificial cerebrospinal fluid (csf) containing neostigmine (5 nM) and/or KCl (100 mM). The basal (non-stimulated) release of acetylcholine (ACh) in the cortex was similar in all experimental groups, whereas KCl stimulated release of ACh was significantly augmented (P < 0.05) in the ipsilateral remaining cortex in lesioned animals that have been implanted with fibroblasts secreting NGF. These results suggest that NGF secreted by genetically engineered fibroblasts modulates neuroplasticity in the adult mammalian CNS and may favour recovery of cortical function following injury.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4gamma, 4delta, 6aalpha, 6agamma, 3a. The lesions were mainly in area 4gamma. In the lesioned hemisphere there were many points around the lesion site (in areas 4gamma and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6agamma) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4gamma, 6agamma and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.     

Response of rat brain indoles and motor activity to short light-dark cycles.

Since the vigilance states of the rat can be largely controlled by one hour light-one hour dark cycles, we investigated the effect of this photoperiod on the rat brain indoles and motor activity. Groups of 9 rats were killed 15-20 min or 45-50 min after the onset of the 1-hour light or 1-hour dark period. Serotonin (5HT) and 5-hydroxyindoleacetic acid were determined fluorometrically in cortex, hypothalamus and brain stem. Tryptophan was determined fluorometrically in serum, cortex and hypothalamus. Cortical tryptophan was highest at the end of the dark period, whereas cortical 5-HT and 5-hydroxyindoleacetic. acid were highest at the beginning of the light period. Motor activity was high during darkness and low during light. When the biochemical results were compared to the motor activity records of the individual animals, the decrease in motor activity at the onset of light correlated significantly with the cortical 5-hydroxyin- doleacetic acid/5-HT ratio in the animals killed at the beginning of the light period. The results indicate a rapid response of the cortical indoles to the onset of light and support the hypothesis that the induction of sleep is related to the brain indole metabolism.     

Monophosphoryl Lipid A and Pam3Cys Prevent the Increase in Seizure Susceptibility and Epileptogenesis in Rats Undergoing Traumatic Brain Injury

Five percent of all epilepsy cases are attributed to traumatic brain injury (TBI), which are known as post-traumatic epilepsy (PTE). Finding preventive strategies for PTE is valuable. Remarkable feature of TBI is activation of microglia and subsequent neuroinflammation, which provokes epileptogenesis. The toll-like receptor agonists monophosphoryl lipid A (MPL) and tri-palmitoyl-S-glyceryl-cysteine (Pam3Cys) are safe, well-tolerated and effective adjuvants existing in prophylactic human vaccines. We examined the impact of early injection of MPL and Pam3Cys to rats, on the rate of kindled seizures acquisition following TBI. Rats received a single dose (1 µg/rat) of MPL or Pam3Cys through intracerebroventricular injection. 5 days later, trauma was exerted to temporo-parietal cortex of rats by controlled cortical impact device. After 24 h, traumatic rats underwent amygdala kindling. Brain level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) was also measured in traumatic rats by immunoblotting. Compared to non-traumatic (sham-operated) rats, traumatic rats showed three times lower seizure threshold (133?±?5 µA vs. 416.3?±?16 µA, p?<?0.001); about three times less number of stimuli to become kindled (5?±?1 vs. 14?±?2, p?<?0.01); longer duration of kindled seizure parameters including entire seizure behavior, generalized seizures, and afterdischarges (p?<?0.001); and a two times increase in the TNF-α level. MPL and Pam3Cys did not change kindling rate and the seizure parameters in sham-operated rats. The MPL- and Pam3Cys-pretreated traumatic rats displayed seizure threshold, speed of kindling, and duration of kindled seizure parameters, similar to the non-traumatic rats. Pretreatment by MPL and Pam3Cys prevented the increase in TNF-α level by trauma. Given that MPL and Pam3Cys currently have clinical use as well-tolerated vaccines with reliable safety, they have the potential to be used in prevention of PTE.     

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.     

Suppression of generalized seizures activity by intrathalamic 2-chloroadenosine application

In the present study, we investigated the effects of micro-injecting 2-chloroadenosine (2-CADO; an adenosine receptor agonist) into the thalamus alone and with theophylline (a nonspecific adenosine receptor antagonist) pretreatment on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in male Wistar albino rats. Following intrathalamic 2-CADO injection alone or theophylline pretreatment, 50 mg kg(-1) PTZ was given ip after 1 and 24 hrs. The duration of epileptic seizure activity was recorded by cortical electroencephalogram (EEG), and seizure severity was behaviorally scored. Intrathalamic 2-CADO administration induced significant decreases in both seizure duration and seizure severity scores at 1 and 24 hrs, but the effects were more abundant on the seizures induced after 24 hrs. On the other hand, pretreatment with theophylline prevented the inhibitor effect of 2-CADO on seizure activity and increased both seizure duration and seizure scores. Present results suggest that the activation of adenosine receptors in the thalamus may represent another anticonvulsant/modulatory site of adenosine action during the course of the PTZ-induced generalized tonic-clonic seizures and provide additional data for the involvement of the adenosinergic system in the generalized seizures model.     

The piriform cortex and the cortical nucleus of the amygdala in epileptogenesis--the role of the rostrocaudal gradient

The seizure susceptibility of amygdaloid complex in rat was investigated. In piriform cortex and cortical nucleus of amygdaloid complex the structural and electrophysiological rostro-caudal differences were found (using relative spectral densities EEG, seizure thresholds, electrical kindling rate). The fundamental dependence of severity of motor seizures from structural (nuclear or cortical) organization of stimulating area was shown. There were more of limbic stages while stimulating anterior and posterior cortical nuclei, and there were more generalized stages while stimulating piriform and periamygdaloid cortex. Using the model of electrical kindling anticonvulsant effects of Sacricin were demonstrated. Sacricin is one of the compounds of polycarbonic acid. Sacricin has fully coped the process of secondary generalization of epileptic seizures.