Cognitive impairments and microvascular endothelial dysfunction in unilateral occlusion of the carotid artery

Gulyaev S.M., Urbanova E.Z.

Institute of General and Experimental Biology of the Siberian Branch of the Russian Academy of Sciences, Ulan-Ude, Russia

Objective. The study was aimed at determining cognitive impairments, vascular endothelial dysfunction and morphofunctional alterations of neurons in brain structures (neocortex and hippocampus) in unilateral occlusion of the common carotid artery in albino rats.

Materials and methods. The experiments were carried out on Wistar albino rats. The animals were divided into two groups: group 1 – the control group composed of sham-operated rats and group 2 – the study group consisting of rats with cerebral ischaemia. The model of cerebral ischaemia was reproduced by occlusion of the left common carotid artery. Cognitive functions in rats were assessed by means of the object recognition test and conditioned passive avoidance response (CPAR). The degree of vascular endothelial dysfunction was evaluated by the number of circulating endotheliocytes and concentration of end products of nitric oxide – nitrites in blood plasma. Pathomorphological studies of the brain and morphometric analysis of the number of damaged neurons after ischaemic exposure were carried out by means of light microscopy.

Results. It was determined that unilateral occlusion of the common carotid artery in rats resulted in memory impairment revealed by the object recognition test and CPAR (p≤0.05). Cerebral ischaemia induced an elevated level of circulating endotheliocytes and a decrease in end products of nitric oxide – nitrates as compared with the controls (p≤0.05). Morphological study demonstrated signs of vasoconstrictive reactions, microvascular endothelial oedema, as well as an increase in the proportion of damaged neurons localized in the fronto-bregmatic region of the cortex of the cerebral hemispheres and hippocampus on the ipsilateral side (p≤0.05).

Conclusions. Unilateral occlusion of the common carotid artery in albino rats resulted in cognitive impairments, damage of neurons in the most vulnerable areas of the cortex of the cerebral hemispheres and hippocampus predominantly on the ipsilateral side. Cognitive impairments and ischaemic lesions of the brain structures are induced by endothelial dysfunction, enhanced desquamation of endotheliocytes and prevalence of vasoconstrictive reactions resulting from decreased production of the major vasorelaxing factor – nitric oxide.

KEY WORDS: atherosclerosis, carotid artery stenosis, cerebral ischaemia, cognitive impairments, endothelial dysfunction, nitric oxide, hippocampus, neurons.

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