THE INFLUENCE OF A NEW INHIBITOR OF NA+/H+ EXCHANGER ON THE POSTREPERFUSION OF THE BRAIN AFFECTION

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Purpose of the work was the investigation of neuroprotective properties of a new inhibitor of Nа+/ H+ exchanger of 1 isoform (NHE-1) of RU-1355 com- pound in the course administration to rats with postre- perfusion affections. Materials and methods of the study: the inves- tigations were carried out using 40 female rats with endovascular 60 minute occlusion with the further reperfusion of the left medium cerebral artery (OL- MCA) (Koizumi, 1986; Longa, 1989; Belayev, 1996). The animals were divided into control: 1-2 groups of sham operated (n=10) and control-ischemia/reperfu- sion (IR) (n=10) - animals without and with OLMCA correspondingly without treatment; and experimental 3-4 groups “IR+substance” to animals with OLMCA injected RU-1355 compound (1.12 mg/kg/day, n=10) and glycine (800 mg/kg/day, n=10) 10 minutes before the reperfusion and during the following 7 days. The study of neurological disturbances was carried out on the 1st, 3rd, and 7th days (Garcia scale) and postperfu- sion damages on the 1st, 3rd, 7th, 14th, 21st, 28th days (adhesive test and tongue protrusion test). Orienta- tional and exploratory behavior and protective reac- tions (open field test) of animals were studied on the 1st, 7th, 14th, 21st, 28th days after the operation. The data were statistically processed with the use of GraphPad. Prism 5.0 program (USA). Results: we have shown, that RU-1355 com- pound and glycine comparison drug in the animals with OLMCA faster restored a neurologic symptoms (Garcia scale), and exceeded the results of the control animals on the 1st day by 17% and 16% correspond- ingly (p<0.05), and equally by 18% on the 3rd day. Test for the tongue discoordination during the whole period of the observation showed that RU-1355 com- pound improved a motion function (augmented the quantity of licked off peanut butter) and approached to the pre-operational level and exceeded the effect in rats which did not receive the substance (p<0.05) and the action of glycine (p>0.05). In the setting of the course injection of RU-1355 compound during 7 days after the occlusion of LMCA the restoration of sensi- tivity disturbance and motor function of a limb with counterlateral side were shown with faster rat release from a gluing strip in adhesion test. The maximum and statistically significant effect of the compounds under study was observed on the 4th and 3rd weeks of post-reperfusion affections. So, while applying RU- 1355 compound we observed the improvement of neurological symptoms for 3 weeks by 36% (p>0.05), and for 4 weeks by 52% (p>0.05) in relation to the animals of control group without a treatment. Glycine showed the similar effect. In the open field test in 24 hour after the occlusion of LMCA in all experimen- tal groups we revealed signified disturbances of be- havioral reactions of rats. Beginning with the second week of post-reperfusion period we noted a relevant positive action of RU-1355 compound and glycine injection which exhibit the gradual normalization of behavioral reactions of the experimental animals. Behavioral reactions in the animal group “ischemia/ reperfusion” did not restored. Conclusions: RU-1355 compound in a course intravenous injection at dose 1.12 mg/kg per day on a model of 60 minute OLMCA with further reperfu- sion conduces the break of fast mechanisms of necrot- ic death, as well as reduces distant consequences of post-perfusion affections of the brain.