Effect of circular RNA, mmu_circ_0000296, on neuronal apoptosis in chronic cerebral ischaemia via the miR-194-5p/Runx3/Sirt1 axis

Chronic cerebral ischaemia (CCI) is a common pathological disorder, which is associated with various diseases, such as cerebral arteriosclerosis and vascular dementia, resulting in neurological dysfunction. As a type of non-coding RNA, circular RNA is involved in regulating the occurrence and development of diseases, such as ischaemic brain injury. Here, we found that HT22 cells and hippocampus treated with CCI had low expression of circ_0000296, Runx3, Sirt1, but high expression of miR-194-5p. Overexpression of circ_0000296, Runx3, Sirt1, and silenced miR-194-5p significantly inhibited neuronal apoptosis induced by CCI. This study demonstrated that circ_0000296 specifically bound to miR-194-5p; miR-194-5p bound to the 3′UTR region of Runx3 mRNA; Runx3 directly bound to the promoter region of Sirt1, enhancing its transcriptional activity. Overexpression of circ_0000296 by miR-194-5p reduced the negative regulatory effect of miR-194-5p on Runx3, promoted the transcriptional effect of Runx3 on Sirt1, and inhibited neuronal apoptosis induced by CCI. mmu_circ_0000296 plays an important role in regulating neuronal apoptosis induced by CCI through miR-194-5p/Runx3/Sirt1 pathway.

Abstract TP194: Relation Between Lipoprotein (a) and Cerebral Arteriosclerosis

Background: Lipoprotein(a) is known to be associated with increased atherosclerotic burden and vascular event. We investigated the relationship between lipoprotein(a) level and cerebral arteriosclerosis burden, including both atherosclerosis and small vessel disease. Methods: Consecutive patients with acute cerebral infarction or transient ischemic attack who had been through both brain imaging and serum lipoprotein a level analysis were included in the study. For cerebral atherosclerosis, intracranial arterial calcification status at cavernous portion of internal carotid artery and cerebral atherosclerosis score as the sum of major cerebral arterial stenosis were measured from brain CT angiography. Assessed cerebral small vessel disease phenotype included white matter hyperintensities, old lacune, cerebral microbleeds and extensive perivascular space. The patients were categorized into four groups according to the predefined cut-off values of lipoprotein(a) (15, 30, 50mg/dL). Results: A total of 990 patients were included with 457 female patients (mean age = 68.2 ± 12.8 years). Overall cerebral atherosclerosis score or total small vessel disease burden was not increased according to increased lipoprotein(a) group, although the proportion of the patients with severe calcification showed increasing tendency. Multivariable logistic regression analysis revealed that increased lipoprotein(a) was independently associated with severe calcification (group 4, odds ratio = 1.68, confidence interval = 1.01 – 2.80). Increased lipoprotein(a) was associated with the presence of white matter hyperintensities and extensive perivascular space, but not associated with old lacune or cerebral microbleed. Conclusion: Lipoprotein(a) is independently associated with severe calcification of intracranial artery. The impact of elevated lipoprotein(a) toward small vessel disease burden seems to be different according to its phenotype.

Pathomorphological examination of hippocampus in the persons of the second period of mature age with cerebral atherosclerosis

The purpose of this research is to study the morphology of the hippocampus in the patients with cerebro-vascular disease with age, sex and somatic types. The study was conducted from autopsy material. The hippocampus male (n=20) and female (n=15) of the patients of the second period of mature age were taken for study. Pathological and anatomical examination showed that all dead people had pathology of brain vessels. Changes specific to the 1 and 2 stages of atherosclerosis were detected in the basilar and middle cerebral arteries. Somatotype was defined with the subsequent calculation of the index by the method of Rees-Eysenck. The morphometric research of right and left hippocampus of the brain has been conducted. The parameters of the hippocampus with the sex were determined. There are presented the results of quantitative and qualitative morphological study of the hippocampus in persons of the second period of adulthood with cerebral arteriosclerosis in various somatotypes. The comparative analysis, of morphometric parameters of the hippocampus of the right and left hemispheres of the human brain, showed, that most significant are the length of the hippocampus width of middle part and width region of legs. On microscopic examination of the hippocampus, the individuals of the second period of mature age, even at the early stages of atherosclerosis of cerebral arteries, are detected dystrophic changes of neurons in the CA1 and CA3 regions, showing their ischemic damage.