Experimental research of cerebroprotective activity of the new 4-aminobutatanoic acid derivative
The aim. To study the cerebroprotective activity of a new derivative of 4-aminobutanoic acid the compound KGM-5 on the effect on survival and behavioural responses, cognitive impairment and neurological deficits in rats with acute cerebrovascular accident.
Materials and methods. Acute cerebrovascular accident (ACVA) was simulated in rats by irreversible unilateral carotid occlusion (UCO) under anesthesia with sodium thiopental (35 mg/kg, intraperitoneally, IP). Five groups of animals were used: intact control (IC, n=6), a group of animals with ACVA, which were not treated (control pathology, CP, n=13); group of animals with ACVA, which were treated for 5 days after surgery (first injection 30 min before surgery) with the compound KGM-5 (ACVA+KGM-5, n=14) at a conditionally effective dose of 30 mg/kg body weight of animals, a group of animals with ACVA (ACVA+CD “Picamilon”, n=13), who received IP for 5 days, the comparison drug (CD) “Picamilon” at a dose of 17 mg/kg and pseudo-operated animals (POA), n=8), which were operated without ligation of the carotid artery, which allows to level the effect of anesthesia and surgery on the studied indicators. The cerebroprotective effect of the studied agents was assessed by an integral criterion – survival of animals (throughout the experiment), indicators of neurological deficit (24, 48, 72, 94 hours after ACVA modelling), the state of cognitive functions in the test of extrapolation escape test (EET) (72 hours after ACVA modelling)
Results. The KGM-5 compound contributed to a significant reduction in the severity of neurological deficit, as evidenced by significant differences in this indicator compared with CP, respectively, the first (0.5 points vs. 1.25 points, p<0.05), the third (0.0 points against 1.0 point, p<0.05) and the fourth day (0.0 points vs. 0.5 points, p<0.05) after OCO. Under the influence of CD “Picamilon” reduction of neurological deficit compared with CP was observed on the first, third and fourth days, but these differences were insignificant (p>0.05). Both studied agents - the compound KGM-5 and CD “Picamilon” contributed to the improvement of cognitive functions of rats with ACVA, as evidenced by a significant reduction (p<0.05) of the latent period of diving in the EET, respectively, 1.8 and 1.7 times compared with CP and did not show a significant effect on animal survival.
Conclusion. The cerebroprotective activity of a new 4-aminobutanoic acid derivative in the conditions of acute cerebrovascular accident in rats was established in terms of the ability to reduce the severity of neurological deficits and improve cognitive functions in the extrapolation escape test. The severity of cerebroprotective activity of the new compound is not inferior to GABA-ergic drug “Picamilon”.
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