Neuroprotective efficiency of creatine-aminoacid complex compound in the model of ischemic stroke in rats

Abstract

Introduction. According to WHO data, stroke and its consequences rank second in mortality after coronary heart disease. Hundreds of clinical trials have yielded only one tool that can be used – intravenous administration of recombinant plasminogen activator, i.e. recanalization agent. The means for effective neuroprotection, despite the huge number of studies, remain not found.The aim of the work was in vivo study of neuroprotective effect of creatine amide (AC-PfA) on neurological and cognitive impairment in a model of ischemic stroke in rats.Material and methods. The model of stroke (FCI) was reproduced by occlusion of middle cerebral artery proximal segment. Neurological deficits were assessed by the latency of movement initiation (LMI), cognitive impairments – by a spatial version of Morris water maze. Four groups of animals were used: (1) negative control (FCI with administration of saline), (2) positive control (FCI with controlled hypothermia), (3) test substance (FCI with administration of AC-PfA) and (4) sham-operated animals.Results. Compared with negative control group, animals восtreated with AC-PfA showed lower latency of movement initiation a day after FCI, what indicates a better functional state of the basal ganglia and associative areas of the cortex. Hypothermia during FCI completely eliminated the effect of increasing LMI. In Morris water maze, animals treated with AC-PfA, in contrast to the negative control group, showed a decrease in platform search time during training, and in a probe trial differed statistically significantly in peripheral searching time and the number of crossings of the platform localization site. Hypothermia was not so effective, although not statistically significantly differs from the group with AC-PfA.Conclusions. A new derivative of creatine has a pronounced therapeutic efficacy in relation to cognitive impairment, and improves the functional state of the systems, controlling the motor activity of animals. At the same time, it exceeds or approaches the effects of hypothermia, known as an effective neuroprotective technique.