ОңТҮстік қазақстан медицина академиясы, хабаршы №4 942, 2021 жыл, том 2



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Discussion 
Hence, gained data revealed that rapamycin caused anticonvulsive action on the PTZ - kindled 
seizures in rats, which was pronounced to prevent generalized clonic-tonic fits. Such effect corresponds with 
other author's data on antiepileptic potency of rapamycin and blocking the mTOR signaling pathway (19). 
Considering mechanisms of antiepileptic effects, it is worth noting that rapamycin is able to inhibit 
tyrosine kinase B [20], which is of importance for vascular endothelial growth factor (VEGF) synthesis and 
neoangiogenesis promotion (3, 17, 19). Newly created vessels are highly porous, and the situation with the 
broking down the brain-blood barrier (BBB) is induced finally (2, 13, 14). The long-term process of 
stimulated neoangiogenesis might be considered as specific pathogenesis of kindled – induced chronic 
seizures (12). Such an assumption corresponds with earlier shown antiseizure effectiveness of axitinib – 
another pharmacon, which caused blocking effects upon tyrosine kinase B activity (6). 
Also, the comparatively high effectiveness of rapamycin, which is equal to the highest dosages of 
sodium valproate, is of great interest. It might be supposed that the ability to inhibit tyrosine kinase B, which 
is essential for the maintenance of kindled seizures (1), is of charge for such effectiveness of rapamycin. 
Conclusion
. Obtained data and analysis of mechanisms of rapamycin effects favor of a possible role 
played by VEGF and remodeling of vessels in PTZ – kindled seizures development.
The pronouncement of action of rapamycin delivered in the highest dosage (3.0 mg/kg, i.p.) 
corresponds to the effects of sodium valproate administered in a dosage of 250.0 mg/kg, i.p. 
 
Financial support
: Ministry of HealthCare of Ukraine. 
Conflict of interests
: there are any conflicts. 


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