Many people suffer from dementia that can be caused by vascular damage. It is known that nitrites can lead to the development of endothelial dysfunction. However, the possibility of development of cognitive impairment after the administration of nitrites is poorly known. The purpose of the study was to determine the morphofunctional state of the brain in rats with chronic nitrite intoxication. Material and methods. The experiment was performed on 32 male WAG rats weighing 180–250 g, divided into four groups. Groups 1 and 2 received 0.1 % and 0.2 % aqueous solution of sodium nitrite, respectively, instead of drinking water (in free access) for 6 weeks. Rats of group 3 were injected 50 mg/kg of body mass same solution intraperitoneally during 2 weeks. Group 4 was the control one. The endothelial growth factor (VEGF–A, pg/ml), the von Willebrand factor (vWF, %), the 2,3–diphosphoglycerate (2,3–DFG, μmol/ml) were measured. Cognitive functions were evaluated using passive avoidance test and extrapolational disposal test. Behavioral reactions were assessed by using “Open field" test. We did the morphological study of brain slices (arterioles, neuropil of the frontal cortex, parietal and occipital lobes of rats) stained with Congo red and staticized our results using non–parametric criteria. Results and discussion. The obtained results showed us that the significant increase of rears and decrease of visiting corners indicate the reduction of anxiety state and significant decrease of looking into the holes suggests the decrease of exploratory activities of rats. In the passive avoidance test the conditioned reflex was not formed in any group. The latency to enter the dark compartment after training was the shortest in group 3. In addition, no experimental group passed the extrapolation disposal test. This result supports the argument that all rats had cognitive impairments. As for biochemical indicators of endothelial dysfunction such as endothelial growth factor, the von Willebrand factor we can see the higher level of these factors in all experimental groups than in control group. We can also notice the same dynamics of the 2,3–diphosphoglycerate that indicated the progress of hypoxia in tissues. During the morphological study we identified that the neuropil was more homogeneous particularly in some places in rats with nitrite intoxication in contrast to control group. We found the damage of endothelium, perivascular edema, the congophilic homogeneous masses subendothelially and the poorly demarcated clump of congophilic masses in the subcortical zone of experimental groups that looked like the amyloid plaque in compare with control group. The worse results were found in rats with intraperitoneal administration of aqueous solution of sodium nitrite. Conclusion. The obtained results showed that the prolonged administration of aqueous solution of sodium nitrite led to the development of endothelial dysfunction, cognitive impairment and subendothelial amyloid deposition with intensive perivascular edema and neural disconnection of the brain in rats.
Keywords: brain, endothelium, nitrites, experiment, amyloid
Full text: PDF (Ukr) 425K