Brain damage and neuronal loss caused by traumatic brain injury, ischemic stroke, and symptomatic status epilepticus can lead to severe long-term consequences, such as impairment in learning and memory and cognitive functions, and development of chronic epilepsy. This can be the result of morphologic and functional changes underlying temporal lobe epilepsy. Epilepsy patients have increased risk of status epilepticus. It is a life-threatening condition when seizures last for more than 30 min and trigger processes leading to neuronal apoptosis and necrosis in various parts of brain. Administration of neuroprotective drugs preventing these pathologic processes could improve the prognosis for such patients. However despite of active research of neuroprotective drugs, the effective ways to prevent brain damage resulting from prolonged seizures are yet to be found. Studies of neuroprotective properties of classic and novel anticonvulsant drugs showed that most of them do not have the sufficient neuroprotective effect and are not able to prevent epileptogenesis. Thus the studies of other potential neuroprotective drugs seem to be promising.

In the late 90-s of the previous century the American Society of Epileptologists defined a priority for research as possibilities to predict a seizure, early determinate and reduct. A method, which would allow the prediction of epileptical seizure's onset based on the EEG data registered with the patient with an epilepsy disease, would also allow implementing the new approach to treatment. If it became reliably possible to predict a moment of seizure, based on the EEG dynamics, one could create an automated closed loop system to prevent a seizure. In the article a number of works regarding this subject were reviewed. Also own results were discussed which were derived from analyses of brain electrical activity of rats with absence epilepsy and with the use of own developed software. Moreover specifics of absence initiation and course were discussed, as well as formation mechanism of thalamus-cortical loop, existing abilities of reduction not only absences, but also cognitive and emotional dissociations. Also described results of analyses of the EEG time series, that were derived by computation of correlation dimension with own developed software.

According to the focal cortical theory of absence epilepsy, spike-and-wave discharges (SWDs) have a cortical focal origin in the perioral region of the somatosensory cortex in rats. In the present study the role of peripheral afferents of the perioral (snout) region in the occurrence of spontaneous SWDs was investigated in the WAG/Rij (Wistar Albino Glaxo from Rijswijk) rat model of absence epilepsy in order to examine whether an input from peripheral sources is imperative for the occurrence of SWDs. Twelve male WAG/Rij rats were chronically equipped with cortical EEG electrodes. Peripheral afferents of the perioral region of the snout nervus trigeminus were pharmacologically blocked with a local injection of 2% Novocain, a blockade of nervus facialis and saline injections were used as controls. ECoGs were recorded before and after bilateral injection of the drug. Blockade of the n. trigeminus decreased the incidence and duration of SWD, while similar injections with Novocain near the n. facialis had no effect. Injections with saline were also not effective. Our data demonstrate that intact peripheral afferent input may be primarily involved in the initiation of SWDs. It suggests that the cortico-thalamo-cortical circuits need the peripheral stimulations from the snout and vibrissae for an initiation of the spontaneous SWDs.

Peculiarities of the formation of primary and mirror (contralateral) epileptic focuses were studied using the model of focal cobalt-induced epilepsy of rabbits. The time intervals for the formation of primary and secondary epileptic focuses in the frontal cerebral cortex of rabbits and generalization of seizure activity were investicated. Fractal analysis was used for evaluation of the electric activity of the cerebral cortex. The anti-seizure activity of the thyrotropin-releasing hormone (TRH) was examined after its intranasal administration in the concentrations of 10(-12) and 10(-9) mol/l. The inhibitory effect of TRH at the concentration studied on the current cobalt-induced epileptic activity of the brain was demonstrated. However, a significant increase in epileptic activity was observed after the intravenous injection of rabbits by TRH in the doses of 25, 50, and 100 mu g/kg.

Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one’s biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides (Rb1 Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

The role of cholinergic nucleus basalis (of Meynert) and the reticular thalamic nucleus in mechanisms of the generation spontaneous spike-and-wave discharges (SWDs) was investigated in the WAG/Rij rat model of absence epilepsy. Selective lesions were affected by local unilateral intraparenchymal infusions of immunotoxin 192 IgG-saporin and cholinotoxin AF64A to the nucleus basalis and the rostral pole of reticular thalamic nucleus. Injections of 192 IgG-saporin into the nucleus basalis increased the number of spontaneous SWDs, while injections in the reticular thalamic nucleus were not effective. Thereby, a loss of cholinergic activity in the nucleus basalis stimulates the appearance of SWDs. At the same time, AF64A infused into reticular thalamic nucleus, besides the reduction of choline acetyltransferase immunoreactive neurons within contralateral nucleus basalis, produced some unspecified lesion of adjacent neuronal tissue, resulted in decrease of number and duration of SWDs as well as in spectral changes in EEG. Considering that the nucleus basalis is an important source of cortical and thalamic cholinergic afferentation, we conclude that cholinergic excitatory input from this structure is important in the control of SWDs in the WAG/Rij rat model of absence epilepsy.

This review focuses on the modeling of status epilepticus in animal brain and modern data on the mechanisms of epileptical seizures initiation using the pilocarpine binding with the muscarinic cholinoreceptors (litium pilocarpine model). The character of epileptics seizures in developing brain and adult brain of rats were investigated. The lines of modulation and inhibition epileptics statues by sacricine and intranasal application of neuropeptide thyroliberin in ultra-low doses are demonstrated. The role of the short-term changes (signal regulated kinase signaling cascade, Kv 4.2 potassium channels, hippocampal and cortical spike-wave discharges) and the long-term changes (loss of selective type of interneurons, excitatory circuits by mossy fiber sprouting) that promotion the epileptic state and recurrent seizures in limbic structure are discussed.

Classical theories on absence epilepsy suggest that a hyperexcitable cortex is a precondition for the occurrence of absence seizures. In the present experiment seizure thresholds and cortical epileptic afterdischarges (AD) were determined in a comparative study of genetically epileptic WAG/Rij, congenic ACI and Wistar rats. Fifteen-second series of low-frequency (8 Hz) stimulation of the sensorimotor cortex were applied in 80- and 180-day-old rats (n= 10-12) with implanted electrodes. Intervals between the stimulation series were at least 10 min, intensity was stepwise increased. Threshold intensities were estimated for movements directly induced by stimulation, AD of spike-and-wave type, clonic seizures accompanying this type of AD and transition into limbic type of AD. Strain differences were found for the threshold for elicitation of stimulus-bound movements reflecting direct activation of the motor cortex, for the threshold of spike-and-wave AD, for maximal clonic intensity of seizures accompanying direct stimulation and AD and for duration of the spike-and-wave AD. ACI's had the lowest thresholds and maximal severity of seizures, whereas WAG/Rij rats had largest duration of AD. Both age and strain differences were found for the transition to the limbic type of AD threshold: WAG/Rij rats had lowest threshold, whereas in Wistar and ACI rats this threshold decreased with age. The decrease of this threshold correlated with the increase of the incidence and total duration of spontaneous SWDs in WAG/Rij rats (R=-0.56, -0,53, p<0.03). It can be concluded that it is not the excitability of the sensorimotor cortex per se that distinguishes genetic epileptic rats from its controls, rather the long duration of spike-wave AD and the lower threshold for spread of epileptic activity into the limbic system.

The origin of generalized absence epilepsy is still not known. In the last century, four theories have dominated the debate about the origin of the bilateral synchronous generalized spike-wave discharges associated with absence seizures: the "centrencephalic" theory [Penfield and Jasper], the "cortical" [Bancaud, Niedermeyer, Luders], the "cortico-reticular" theory [Gloor, Kostop[oulos, Avoli] and the "thalamic clock" theory [Buzsaki]. There is now some evidence that absence epilepsy, as studied in the WAG/Rij model, is a corticothalamic type of epilepsy. A new hypothesis is proposed which suggests that a cortical focus in the somatosensory cortex is driving the widespread corticothalamic networks during spontaneous absence seizures. This modern theory was given the name "hot spot' theory" [Meeren et al., 2002]. According to the present view three brain structures are critically involved and their integrity seems a minimal and sufficient condition for the occurrence of spike-wave discharges. Firstly, the reticular thalamic nucleus is involved and most likely its rostral pole. Secondly, the thalamocortical relay cells in the ventrobasal complex play a role and, thirdly and most importantly, the cerebral cortex with its epileptic zone. The zone in which the epileptic focus seems to be localised is located on the somato-sensory cortex, and more precisely in the area on which the peri-oral region including the upper lip, projects.

Spontaneously occurring spike-wave discharges (SWDs) and serum concentrations of ovarian steroid hormones were investigated before, during and after pregnancy in WAG/Rij rats, a rat strain with genetically determined absence seizures. Eight groups of rats were included in the assays of progesterone and estradiol: rats at diestrus, at various days of pregnancy and at lactating days while EEG's were recorded at the same days in rats equipped with cortical EEG electrodes. Serum concentration of progesterone was 3-fold increased at the 3rd day of pregnancy and remained elevated till the 18th day of pregnancy, thereafter it returned to control values before delivery. Estradiol was elevated only at the 18th day of pregnancy. The number of SWDs were decreased from 3rd up to 18th days of pregnancy and progressively increased to control level 2 days before parturition. Thereafter a new decrease was found 2-3 after giving birth. These results demonstrate that the changes in plasma progesterone concentration corresponds to the changes in number of SWDs and have a similar time-course. It can be concluded that an increased level of progesterone that occur during pregnancy is associated with a decreased number of SWDs. However, the relationship between SWDs and concentration of progesterone found here is opposite to non-pregnancy data and an antiepileptogenic reaction might have taken place.

Frontoparietal cortex and the thalamocortical circuit comprising reticular thalamic nucleus (RTN) and relay nuclei of the ventrolateral thalamus (VLT) are critical structures in the generation of spike-wave discharges (SWD) during absence seizures. The activity of these nuclei is under the control of the ascending cholinergic projections of nucleus basalis of Meynert. The aim of our study is to make an attempt to change the pattern of SWD in WAG/Rij rats by injecting of cholinotoxine AF64A to the area of RTN. Spontaneous SWD were registered in cortex of WAG/Rij rats with genetically determined absences. The spectral content of SWD was analyzed by means of the Fast Fourier Transformation (FFT) procedure. Unilateral injections of AF64A (1 nmol) to RTN led the decrease in duration and number of SWD comparing to the basal EEG recordings 2 days after the lesion. The FFT analysis showed the disappearance of 17-18 Hz spike on the side of the lesion compared with the intact side. The immunohistochemical study for acetylcholinetransferase (ChaT)-containing neurons showed the loss of ChaT-positive cells in the nucleus basalis area on the side of the lesion. The removal of cholinergic afferentation of RTN and cortex from nucleus basalis inhibits the SWD developing most likely due to the decrease of cortical excitability. Moreover, possibly cholinergic transmission is involved in the transforation of the synchronized phenomena (SWD) to another with close mechanism of generation.