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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.

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.

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.

In addition to the well-known activities of TRH (stimulation of respiration, antidepressant action, increase of motility, antishock action, therapeutic effects against ataxia, and so forth), some new properties were established. TRH was found (1) to stimulate the contractility of lymph vessels in ultra-low doses and to be useful in the treatment of acute pancreatitis; (2) to normalize cerebral circulation in rats and neonates after asphyxia; (3) to improve the electrophysiological parameters of the retina and pigmented epithelium in rats and man, to exert a long-term positive influence on the health status of patients suffering from senile retinal macular dystrophy; (4) to potentiate the analgesic effect of low doses of morphine in a definite range of doses (analog PR-546). It is of paramount importance that most of the indicated activities of TRH may hold promise for clinical application.

The integral rat brain temperature was measured by radiothermoscope after intranasal instillation of thyroliberin in a dose 400 mkg. The recording increase of temperature lasted during two hours after instillation. This phenomenon is based both on the direct action of thyroliberin and on its capacity to stimulate the induction of other regulatory peptides.

The individual peculiarities of functional changes in motor asymmetry determined by behavioral test in T-maze have been shown in experiments with rats (nonpedigree and line LATI). The application of thyroliberin (10 mkg/kg) causes and increases the left-side lateralization which introduces alteration in the individual strategy of the successive round of 12 rays of radial maze with food during solution of spatial orientation task.

The influence of TRH (100 micrograms/kg) and ACTH4-7 Pro-Gly-Pro (15 micrograms/kg and 25 micrograms/kg) involved an acceleration of the spatial learning on the 12-arm radial maze and on T-maze in rats; an increase in the number of correct choice after short (5-10 min) retention interval; and affected the working and reference spatial memory in the test of reinforced place performance. The effects of the TRH and ACTH4-7 Pro-Gly-Pro did not interfere with one another.