Brain D2-Like Dopamine Receptor Distribution in Rats with Different Types of Genetic Epilepsy.

The distribution of the D2-like dopamine receptor (D2DR) in the cortex and striatum was compared between rats with absence, audiogenic, or combined genetically determined epilepsy and normal Wistar rats by autoradiography. A significantly lower D2DR binding density was observed in the dorsal and ventrolateral aspects of the nucleus accumbens in epileptic vs. non-epileptic rats. Rats with audiogenic epilepsy additionally showed a higher D2DR density in the dorsal striatum and motor and somatosensory cortex and a lower D2DR density in the ventrolateral part of the nucleus accumbens. The findings indicated that a common neuronal circuit is involved in the pathogenesis of both convulsive and nonconvulsive forms of generalized epilepsy.

Structural alterations in the rat brain and behavioral impairment after status epilepticus: An MRI study.

Temporal lobe epilepsy (TLE) is one of the most common neurologic disorders often associated with behavioral impairments and cognitive deficit. Lithium-pilocarpine model of seizures in rodents reproduces many features of human convulsive status epilepticus (SE) and subsequent TLE. In this study, we have investigated changes in the rat brain after lithium-pilocarpine SE using a high-field MRI system for small animals in early and chronic periods after SE. We have studied the relationship between T2 relaxation time measured in these periods and the development of behavioral exploratory response to novelty and habituation in the open field test. A significant increase in T2 in the hippocampus and associated structures was found 2 days after SE and practically resolved by day seven, while an increase in T2 in the parietal and prefrontal cortex appeared 30 days after SE. High T2 values in the parietal cortex and thalamus on day two after SE were associated with an increased mortality risk. A substantial variability in T2 relaxation time was observed in the hippocampus and amygdala 30 days after SE. Rats survived after SE showed locomotor hyperactivity and disruption of long-term habituation in the open field test carried out 5 weeks after the seizures. Interestingly, T2 in the amygdala 30 days after SE had a strong correlation with hyperactivity in the novel open field. Therefore, the amygdala damage may be an important factor in the development of hyperactivity in the chronic period after SE.

[The Role of Blood-Brain Barrier in the Development of Childhood Febrile Seizures and Temporal Lobe Epilepsy.]

Blood-brain barrier (BBB) of the central nervous system (CNS) is a physiological barrier that makes it possible to control the exchange of ions, molecules and cells between blood and tissue and to prevent their free inflow into the brain. BBB is crucial for maintenance of brain homeostasis. BBB damage accompanies many degenerative, neurological and inflammatory (infectious or noninfectious) diseases and pathological states. Current review reports about BBB role in development of childhood febrile seizures and temporal lobe epi- lepsy.

[Neuroprotection in epilepsy].

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.

The role of perioral afferentation in the occurrenceof spike-wave discharges in the WAG/Rij modelof absence epilepsy.

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.

[A perspective of present approaches to EEG analyses performed with intention to find seizure predictors].

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.

[Neuropeptide thyroliberin in ultra low doses--anticonvulsant defense of the brain]. / Neiropeptid tiroliberin--protivosudorozhnaia zashchita mozga v sverkhmalykh dozakh.

Thyroliberin (TRH) promoting endogeneous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application). This application of TRH in ultra-low doses contrast the method of systemic TRH administration in the large doses). In our experiments intranasal application of 10(-8), 10(-10) and 10(-12) mol/l TRH significantly inhibited the severe epileptic motor fits in rats induced by PTZ. EEG also confirms beneficent effect of TRH (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide His-Pro (10(-10), 10(-8) mol/l). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology.

[Neuropeptide thyroliberin--an endogenous anticonvulsant in the brain]. / Neiropeptid tiroliberin--éndogennaia protivosudorozhnaia zashchita mozga.

Thyroliberin (TRH) promoting endogenous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application. This application TRH in ultra-low doses contrast the method of systemic TRH administration (i.v., i.m. or oral in the large doses--mg). In our experiments intranasal application of 10(-9) M, 10(-10) M and 10(-12) M TRH significantly inhibited the severe epileptic motor fits in rats induced by pentylenetetrazole (PTZ). Beneficent effect of TRH is also confirmed by EEG (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide cHis-Pro-NH2 (10(-10) M, 10(-5) M). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology.

[The neuropeptide galanin and the seizure reactions of the developing brain]. / Neiropeptid galanin i sudorozhnye reaktsii razvivaiushchegosia mozga.

In this work polyfunctional peripheral (pancreas) and central effects of galanin 1-29 (gal.) were reviewed. In hypothalamus gal. exerts neuroendocrine effects through modulation of secretion of principal hormones of hypophysis, co-localized with acetylcholine in some brain structures including hippocampus. Gal. influences behaviour and memory. Newest hypotheses of T. Hokfelt and J. N. Crawely [correction of G. Crowly] on the involvement of gal. to pathogenesis of in Alzheimer disease and possibilities of its clinical antiamnestic utility are discussed. Our own data indicates antiseizure effect of gal. in the model of febrile convulsions in children--hyperthermia induced seizures in neonatal rats in the age from 5 to 13 days. Systemic intraperitoneal administration of gal. was effective in certain age--7-11 days of postnatal period--in preventing hyperthermia induced seizures: in increased by 2-3 times latency of minimal seizures and clonic-tonic generalized seizures. In adults rats gal. showed antiseizure action when administered intranasal in the model of pentilenetetrazol seizures (modified test with repeated administration of subthreshold doses). Modern data on structure and function of galanin, its chimeric analogs and galanin receptors receptors are discussed.