THE EFFECT OF PIR-20 COMPOUND ON COGNITIVE DEFICIT REDUCTION IN EXPERIMENTAL GLOBAL CEREBRAL ISCHEMIA IN RATS

A study was conducted to assess the effect of a new pyrimidine derivative PIR-20 (50 mg/kg) on the development of cognitive deficits in the conditions of global cerebral ischemia in rats. The study was performed on 40 male Wistar rats weighing 200–220 g, divided into 4 groups of 10 individuals. False-operated rats and negative control animals were injected with a suspension of purified water and tween-80, the third group of animals received Cavinton (3,2 mg/kg), the fourth — PIR-20 (50 mg/kg). All test subjects were injected intraperitoneally for ten days prior to surgery. The number of dives increased to 100%, while the decision-making time decreased by 55,2% (p<0,05) in the extrapolation escape test against the background of the PIR-20 compound administration. 75% of the animals treated with PIR-20 did not re-visit the dark compartment, and the time of entering the dark chamber increased by 172,9% (p<0,05) as compared to the group of negative control rats in the test of passive avoidance of the avesir environment. It was confirmed that the studied compound PIR-20 contributes to the improvement of cognitive and mnestic functions, which is confirmed by the results of tests of passive and active aversive environment avoidance. The obtained effect exceeded the results of the control group and the reference drug Cavinton.

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”.

ADHD-like behaviour in the offspring of female rats exposed to low chlorpyrifos doses before pregnancy / Ponašanje nalik ADHD-u u potomaka ženki štakora izloženih niskim dozama klorpirifosa prije trudnoće

The aim of this study was to investigate how chronic low-dose chlorpyrifos exposure of female Wistar rats before and during pregnancy affects behavioural parameters in their offspring. Four months before pregnancy, we exposed three groups of rats to chlorpyrifos doses of 5, 10, and 15 mg kg-1 body weight every day for 30 days, whereas one group received a single 30 mg kg-1 dose on gestational day 6. When the offspring of the exposed rats grew up, we studied their anxiety rate, motor activity, and cognitive abilities using the respective behavioural tests: open field test, dark/light box, and the extrapolation escape test. The offspring of rats exposed before pregnancy had significantly higher activity rate than controls, and even showed motor agitation and hyperactivity signs. The offspring of rats exposed to the single dose had difficulties solving the extrapolation escape test and showed poorer short- and long-term memory performance. This confirmed that even pre-pregnancy chlorpyrifos exposure can cause neurobehavioral consequences in offspring. Even though the mechanisms of the observed changes remain unclear and need further investigation, these data seem alarming and may serve as an important argument for revising the terms of safe pesticide use