Role of lipid metabolic disturbances for the mechanisms of immune dysregulation and endothelial dysfunction in early forms of chronic cerebrovascular insufficiency

It is known that the immunological component of nearly any dysregulatory pathology is manifested by the development of new functional systems providing adaptation reactions, as well as by the presence of allostasis, reflecting other forms that are different from the normal parameters, and variants of mutually supporting relationships that occur at different structural and functional levels of the body. A long stay in the areas of military campaigns inevitably has a negative impact on the re-adaptation for civilian life, and it is accompanied by occurence of pathological functional connections that lead to dysregulation of the basic functions, including those of nervous and immune systems. In this regard, we studied the features of immune cell functioning in the patients with early forms of chronic cerebral ischemia accompanied by hyperlipoproteinemia, and we have made a comprehensive assessment of the factors characterizing morphological and functional state of endothelium. A representative survey included 87 patients who participated in the Afghan campaign with early forms of cerebral circulatory failure. The subjects exhibited objective and subjective signs of underlying vascular disease, typical to the earliest manifestations of chronic cerebrovascular insufficiency (CVVN) manifesting as headache, dizziness, noise in the head, memory impairment, decreased performance. All the patients underwent a comprehensive examination, i.e., expanded lipidogram, determination of vasoactive factors in the blood and cultural fluid, the number of circulating desquamated endotheliocytes, thus reflecting morphological signs of endothelial damage, additional ultrasound Doppler sonography of the main vessels, transcranial Doppler and electroencephalography were carried out.

It is known that endothelial cells are independently capable of modulating vascular tone, depending on the current clinical condition, and it may be also subjected to remodeling rearrangements with involvement into the pathological process, e.g., in atheromatosis. In this regard, endothelial dysfunction is a key factor in developing vascular pathology, affecting the systemic level. According to results of the study, it has been established that the main progression mechanism for the early forms of CVVN is the development of endothelial dysfunction. The condition has multifactorial genesis in which immune mechanisms are directly involved. Hyperlipoproteinemia established in more than 90% of cases, is one of the most important metabolic triggering factors for development of immune reactions, which is also promoted by imbalance of vasoform and thrombogenic factors, by presence of oxidative and nitrosative cellular stress markers which generally contribute to increase in cerebral vascular remodeling and the basis for the formation of organic pathology of the central nervous system.

1. Altman D.Sh., Davydova E.V. On the role of autoimmune mechanisms in the progression of early forms of chronic brain ischemia. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (16), no. 2-3 (1), pp. 18-20. (In Russ.)

2. Greenstein A.B., Schneider N.A. Cerebrovascular complications of arterial hypertension. Krasnoyarsk: Krasnoyarsk State Medical Academy, 2002. 160 p.

3. Diagnosis and treatment of hypertension. Russian recommendations (fourth revision). Sistemnyye gipertenzii = Systemic Hypertension, 2010, no. 3, pp. 5-26. (In Russ.)

4. Yemchenko N.L., Tsyganenko O.I., Kovalevskaya T.V. Universal method for the determination of nitrates in the biological media of the body. Klinicheskaya laboratornaya diagnostika = Russian Clinical Laboratory Diagnostics, 1994, no. 6, pp. 19-20. (In Russ.)

5. Koval S.N., Miloslavsky D.K., Snegurskaya I.A. Therapeutic angiogenesis in diseases of internal organs - opportunities and prospects. Visnik problem biologii i meditsini = Bulletin of Biological Problems and Medicine, 2013, Vol. 1 (104), Iss. 4, pp. 20-27. (In Russ.)

6. Korobeynikova E.N. Indicators of lipid metabolism in the serum of a practically healthy population living in the South Ural region in terms of adaptation to climatic and man-made influences: guidelines. Chelyabinsk, 2002, pp. 40-43.

7. Schmidt E.V. Classification of vascular lesions of the brain and spinal cord. Zhurnal nevropatologii i psikhiatrii = Journal of Neuropathology and Psychiatry, 1985, no. 9, pp. 1281-1288. (In Russ.)

8. Berridge M.V., Herst P.M., Tan A.S. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol. Annu. Rev., 2005, Vol. 11, pp. 127-152.

9. Felten D., Maida M.E. Psychoneuroimmunology // in book: Encylopedia of the human brain. Ed.-in-cnief V.S. Ramachandran. Academic Press, 2002, Vol. 4, pp. 103-127.

10. Gorelick P.B. Lipoprotein-associated phospholipase A2 and risk of stroke. Am. J. Cardiol., 2008, Vol. 101, no. 12A, pp. 34F-40F.

11. Hladovec J., Prerovsky I., Stanek V. Circulating endothelial cells in acute myocardial infarction and angina pectoris. Klin. Wochenschr., 1978, Vol. 56, pp. 1033-1036.