ADEMOL INFLUENCE ON STEROID NEUROTOXICITY FORMATION BY CORTISOL LEVEL UNDER CONDITIONS OF MODELLED CRANIOCEREBRAL INJURY

Abstract

One of the cellular targets for pathogenetic influence on the course of traumaticbrain injury (TBI) is the use of pharmacological agents that are able to counteract thenegative effects of excess concentrations of glucocorticoids (glucocorticoid neurotoxicity)on the brain neurons in cerebral pathology.The goal of the work.To evaluate the effect of adamantane derivative 1-adamantylethyloxy-3-morpholino-2-propanol hydrochloride (Ademol) in comparison with amantadine sulfateand 0.9% NaCl solution on the formation of steroidal neurotoxicity in rats with acute TBI.Material and methods. The therapeutic effect of Ademol in rats with TBI was evaluatedwith a dose of 2 mg/kg (i\v) every 12 hours for 8 days. The pseudoperated animals andcontrol group received 0.9% NaCl solution at a dose of 2 ml/kg (i\v), and the comparisongroup received amantadine sulfate at a dose of 5 mg/kg in the same mode. Cortisol levelswere used to determine the efficacy of the test drugs in TBI.Results. Applied pharmacotherapy in the form of ademol and amantadine sulfateprevented an increase in the blood cortisol levels of TBI animals, but its effectivenessdepended on the drug selected. In rats treated with ademol (2 mg/kg), the level of cortisolin the blood ranged from 179 to 188 ng/ml (P5-P95) and was 2.58-fold lower (p<0.05)compared to control pathology group. However, the effect of amantadine sulfate (10 mg/kg) on the level of cortisol in the blood of the sagittal sinus was significantly less thanthat of ademol. Under these conditions, the concentration of cortisol in the blood rangedfrom 271-280 ng/ml (P5-P95), was 1.73 times lower (p<0.05), compared with the controlpathology group, and 49.2% (p<0.05) exceeded the corresponding value in animalstreated with ademol.Conclusions. Therapeutic treatment of rats with severe TBI with a solution of 2 mg/kgademol dose, preferably better than rats in the control pathology group with 0.9% NaCland the group with amantadine sulfate promotes the formation of steroid neurotoxicityby cortisol, with overdose being cortisol the drug averaged 49.2% (p<0.05). One of thepathogenetic mechanisms of the brain protective action in TBI is the ability of Ademolto correct the formation of steroidal neurotoxicity by cortisol levels in severe cerebraltrauma.