[01] Maria N. Starodubtseva, Department of Medical and Biological Physics, Gomel State Medical University, Gomel, Belarus. [02] Natallia V. Halinouskaya, Department of Neurology and Neurosurgery, Gomel State Medical University, Gomel, Belarus. [03] Nadezhda M. Halubykh, Research Laboratory, Gomel State Medical University, Gomel, Belarus. [04] Evgenii V. Voropaev, Research Laboratory, Gomel State Medical University, Gomel, Belarus. [05] Vasiliy B. Smychek, National Science and Practice Centre of Medical Assessment and Rehabilitation, Gorodische, Belarus.

Reactive nitrogen species are well known to be important participants of cerebral stroke development. Low concentration of NO is produced by constitutive NO-synthase under physiological conditions, whereas high concentration of NO is produced by inducible NO-synthase of the stimulus-activated cells of the immune system and endothelium. Based on the concept of two cell states (resting and activated) with different NO production rates we have analyzed NO metabolite (NOx) concentration in plasma of patients with transient cerebral microcirculatory disturbances (TCMD) simultaneously with the levels of inflammatory markers (superoxide dismutase activity and concentration of interleukins (IL-6 and IL-8) and C-reactive protein) and studied the effect of a standard 10-day therapeutic course on them. The sample of patients with TCMD included 24 patients with transient ischemic attack (TIA) and 19 patients with acute hypertensive encephalopathy (AHE). The NOx concentration was measured by the modified Griess method. The presence of two groups with low and high NOx concentration in plasma was detected for the studied sample both in the beginning and in the end of patient’s hospital stay (high NOx plasma samples were found in 18% of cases on Day 1 and 27% of cases on Day 10). The majority of subjects with high plasma NOx concentration on Day 1 were AHE patients (63%) and on Day 10 were TIA patients (78%), correspondingly, The high NOx plasma samples were associated with low superoxide dismutase activity (p=0.045) and increased IL-6 level (p=0.003). Our study’s results suggest that the analysis of NOx concentration changes during a therapeutic course is useful for improving the diagnosis and future prognosis of patients with TCMD.

Stroke, Cerebral Hypertension, Transient Ischemic Attack, Peroxynitrite, Nitrite/Nitrate Ions, Interleukin-6, C-Reactive Protein

[01] Carden DL, Granger DN: Pathophysiology of ischemia-reperfusion injury. J Pathol 2000, 190:255-266. [02] Chen X, Chen H, Xu M, Shen J: Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury. Acta Pharmacologica Sinica 2013, 34: 67-77. [03] Cieślak M, Wojtczak A, Cieślak M: Relationship between the induction of inflammatory processes and infectious diseases in patients with ischemic stroke. Acta Biochimica Polonica 2013, 60(3): 345–349. [04] Gupta HV, Farrell AM, Mittal MK: Transient ischemic attacks: predictability of future ischemic stroke or transient ischemic attack events. Ther Clin Risk Manag 2014, 10:27-35. [05] Jiang Z, Li C, Arrick DM, Yang S, Baluna AE, Sun H: Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia. PLoS ONE 2014, 9(3):e93134. [06] Jickling GC, Zhan X, Stamova B, Ander BP, Tian Y, Liu D, Sison SM, Verro P, Johnston SC, Sharp FR.: Ischemic transient neurological events identified by immune response to cerebral ischemia. Stroke 2012, 43:1006-1012. [07] Kar S, Kavdia M: Endothelial NO and O2− production rates differentially regulate oxidative, nitroxidative, and nitrosative stress in the microcirculation. Free Rad Biol Med 2013 63 (2013) 161-174. [08] Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease: Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014, 45:2160-2236. [09] Matata BM, Galinanes M: Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappaB DNA binding activity. J Biol Chem 2002, 277(3): 2330-2335. [10] Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007, 87:315-424. [11] Sirota TV, Lange NV, Kosiakova NL, Vanichkin AV, Kondrashova MN: New application of adrenalin oxidation reaction for estimation of pro-anti-oxidant properties of bioactive substances. Curr Topics Biophys 2000, 24(2): 185-189. [12] Starodubtseva MN, Kavalenka AI, Petrenyov DR, Cherenkevich SN: Effects of peroxynitrite on morphology and functions of neutrophils. Handbook of free radicals: formation, types and effects. еd.: D. Kozyrev, V. Slutsky. Hauppauge, New York: Nova Science Publishers Inc 2010, 478-503. [13] Szabo C: Multiple pathways of peroxynitrite cytotoxicity. Toxicol. Lett 2003, 140-141:105-112. [14] Van Rooy MJ, Pretorius E: Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke. Thromb Res 2015, 135(3):434-442. [15] Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C: Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 2009, 6(9): e1000145.