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Objective: To quantify genome-wide DNA methylation in the olfactory bulbs, fronto-parietal and occipital regions, and cerebellum in normal male Wistar rats and in modeling incomplete cerebral ischemia caused by permanent bilateral occlusion of the common carotid arteries., Material and Methods: The study was performed on 23 male Wistar rats divided into groups: «Sham operation» and «Cerebral ischemia». The level of genome-wide methylation of CCGG sites was determined by methyl-sensitive restriction using MspI/HpaII endonucleases followed by densitometric analysis of electrophoregrams by ImageJ software., Results: Incomplete cerebral ischemia on the 7th day leads to 56.3% (95% CI: 33.2-76.90) mortality. In the surviving rats of the «Cerebral ischemia» group, compared with the animals of the «Sham operation» group, a pronounced neurological deficit was observed, which was accompanied by changes in the level of whole-genome DNA methylation in the nervous tissue of brain structures ( p <0.05). Incomplete cerebral ischemia in male Wistar rats was characterized by interhemispheric asymmetry in the severity and direction of the epigenomic reaction of the nervous tissue in both ischemic and non-ischemic areas of the brain., Conclusion: It is likely that it is precisely this dynamics of changes in the status of genome-wide DNA methylation in the nervous tissue that imparts plasticity to neuronal function during ischemic damage.

The enrichment of angioneurology with fundamental advances leads to the understanding of new important facets in the pathogenesis of cerebral ischemia. The knowledge of epigenetic mechanisms in the development of stroke, in particular, DNA methylation, which makes a significant contribution to the development and formation of cerebral damage, is becoming more and more relevant. This review reflects an analysis of animal studies proving the relationship of DNA methylation with cerebral ischemia. As a result of the search work, 282 articles from the PubMed database were selected for keywords that corresponded to this topic. Of these publications, 8 studies were devoted to genome-wide DNA methylation, and 6 published the results of DNA methylation of candidate genes in experimental cerebral ischemia. The results have demonstrated that brain DNA methylation in animals is associated with the development of ischemic stroke and may play a role in several pathogenetic mechanisms. In two studies, a decrease in the level of DNA methylation in 2 genes in ischemic brain tissues of laboratory animals was found, at the same time, in four studies, 8 genes, in which methylation increased after ischemic stroke, were reported. These data suggest that the assessment of the level of DNA methylation in stroke is a promising biomarker for the search and improvement of pharmacological and non-pharmacological methods for limiting brain damage in ischemic and reperfusion injury at the stages of preclinical and clinical studies.

Background: The gene encoding apolipoprotein E (APOE) has been proposed as a candidate gene for vascular complications in Type I diabetes. This study aimed to investigate the influence of three-allelic variations in the APOE gene for the development of diabetic retinopathy and nephropathy., Results: Neither APOE alleles frequencies or APOE genotypes frequencies differed between Type I diabetic groups either with or without nephropathy. Similar results were found for patients with and without diabetic retinopathy., Conclusions: APOE gene polymorphism does not determine genetic susceptibility for the development of diabetic retinopathy in Type I diabetes patients. Association between APOE gene polymorphism and diabetic nephropathy may be weak or moderate, but not strong.

Complications of insulin-dependent diabetes mellitus (IDDM) are a major cause of morbidity and mortality; however, the mechanisms of their development are still to be elucidated. Genetic susceptibility contributes to the pathogenesis of nephropathy in IDDM. Enhanced G-protein activation, a cellular phenotype observed in cultured cells from patients with essential hypertension, was recently documented in IDDM subjects with nephropathy. A C825T polymorphism was recently described in GNB3, the gene encoding the beta 3 subunit of heterotrimeric G-proteins. This genetic variant has been associated with enhanced G-protein activation. The 825T allele was observed more frequently in a group with essential hypertension. We analyzed the role of the C825T polymorphism in the predisposition to diabetic complications in IDDM. In this study, we investigated the frequency of this polymorphism in a large case-control study and found no association of the 825T allele with diabetic nephropathy, retinopathy, and neuropathy.