ИСТИНА

The understanding of physiology and genetic principles of human seizure states as well as of systemic level of epileptogenesis mechanisms needs the analysis of biological models. Among models elaborated those which provoke seizures by electric shock or by pharmacological agents (pentilenetetrazol, kainic acid etc.) are most frequently used. Although, the genetic seizure models exist as well. The rats of Krushinsky-Molodkina (KM) strain, bred in Moscow University at the end of 1940s, are the audiogenic seizure (AS) prone animals – the intense seizures are provoked in these animals by exposure to loud sound. KM strain is maintained as inbred (more than 50 generations) and reveals about 100% of penetrance and expressivity – the tonic seizures of maximal intensity develop in almost all animals of a given generation. AS fits (scored by intensity using the arbitrary scale) have some advantages in comparison to electrically or pharmacologically induced seizures, as they could be induced repeatedly and they could be used to evaluate the long-term treatment effects. The AS fits are initiated in the brain stem and they show some differences from ―kindling‖ seizures in pharmacological sensitivity. Rats of KM strain are characterized by very short latency (5-7 s) of clonic-tonic seizure development and by the development of the postictal catalepsy. The repeated (during 18-20 days) sound exposures induce the myoclonic seizures in these animals, which developed in limbic system and resemble typical kindling seizures. The prolonged (15 min) exposure to alternating short (10 s) periods of loud and weak sound induce the brain vessels disturbances in KM rats which could be detected behaviorally as palsies and paresis of extremities. AS strains in general (and KM rats in particular) are characterized by decreased brain stem GABAergic function with the concomitant increase in glutamatergic excitability as well as by shifts in brain catecholamine‘s levels. Initially the patterns of deviations in physiological and neurochemical indices were compared to those of the ―initial‖ Wistar strain, although at present these comparisons are performed using two new strains (derived from KM x Wistar hybrids which are now bred for more than 30 generations). They are: strain ―4‖ (with maximal AS intensity) and strain ―0‖ (lack of seizures in response to sound). These strains together with KM strain share more or less common genetic background and this open the possibility to explore the influence of this factor as well (i.e. when comorbidities of AS and other pathological traits- anxiety and depression - were analyzed). Such strain ―triad‖ is unique and is not used in other laboratories analyzing AS.