Imbalance of the hemocoagulation and fibrinolysis systems under conditions of diabetes mellitus complicated by acute circulatory disturbance in the pool of carotid arteries of rats
Keywordsdiabetes mellitus, cerebral ischemia-reperfusion, hemocoagulation, fibrinolysis
Introduction. Both cerebral ischemia and diabetes mellitus (DM) are evidenced to be associated with hypercoagulation state, though today the facts concerning hemocoagulation condition with diabetes mellitus complicated by cerebral ischemia-reperfusion are lacking.
The aim of the study. To examine the dynamics of interrelations between the pro-, anticoagulant and fibrinolytic parameters in rats with diabetes mellitus complicated by acute cerebral circulatory disturbance.
Results. At the early ischemic-reperfusion period activation of the pro-coagulant potential (decrease of prothrombin and thrombin time and increase of fibrinogen content) is found to be balanced by a reduced activity of XIII factor and an increase activity of antithrombin III in rats without diabetes mellitus. At the same period in rats with diabetes increase of the pro-coagulant potential is accompanied by the activation of XIII factor and a reduced activity of antithrombin III promoting clot formation. On the 12th day of the observation the parameters of the coagulation chain in the hemostasis system and antithrombin III return to the level of the control animals in rats without diabetes, but in rats with diabetes the factors of intensification of a thrombotic risk remain activated.
At the early and late ischemic-reperfusion periods the parameters of blood fibrinolytic activity increase in rats without diabetes; in animals with diabetes mellitus the parameters of fibrinolytic activity remain without changes at the early period of observation (except decrease of a potential plasminogen activity), and they decrease on the 12th day of the post-ischemic period, which deteriorates conditions of thrombolysis.
Conclusions. Complication of diabetes mellitus by ischemic-reperfusion lesion of the brain results in imbalance in the hemocoagulation system at the expense of intensification of pro-coagulant mechanisms, and promotes inhibition of fibrinolytic processes with advanced changes in the dynamics of observation.
Goldman S, Prior SM, Bembenek JP, Niewada M, Broniatowska E, Członkowska A, et al. Activation of blood coagulation and thrombin generation in acute ischemic stroke treated with rtPA. J Thromb Thrombolysis. 2017;44(3):362–70. doi: 10.1007/s11239-017-1544-7
Bembenek JP, Niewada M, Siudut J, Plens K, Członkowska A, Undas A. Fibrin clot characteristics in acute ischaemic stroke patients treated with thrombolysis: the impact on clinical outcome. Thromb Haemost. 2017;117(7):1440-7. doi: 10.1160/TH16-12-0954
Zhao Y, Zhang J, Zhang J, Wu J. Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values. PLoS One [Internet]. 2011[cited 2019 Jan 12];6(1):e16470. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030587/pdf/pone.0016470.pdf doi: 10.1371/journal.pone.0016470
Binay C, Bozkurt Turhan A, Simsek E, Bor O, Akay OM. Evaluation of Coagulation Profile in Children with Type 1 Diabetes Mellitus Using Rotational Thromboelastometry. Indian J Hematol Blood Transfus. 2017;33(4):574-80. doi: 10.1007/s12288-017-0793-0
Tkachuk OV. Influence of streptozotocin-induced diabetes and incomplete global ischemia of the brain onto apoptosis in thymus of rats. Fiziolohichny zhurnal. 2011; 57(6): 58-64.
Skibo G.G. Ispolzovanie razlichnikh eksperimentalnikh modelei dlia izucheniia kletochnikh mechanizmov іshemicheskogo porazheniia mozga. Patologija. 2004; 1(1): 22-30.
Mahalyas VM, Mikhyeyev AO, Rohovyy YuYe. Suchasni metody eksperymental'nykh ta klinichnykh doslidzhen' tsentral'noyi naukovo-doslidnoyi laboratoriyi Bukovyns'koyi derzhavnoyi medychnoyi akademiyi. Chernivtsi; 2001. 42 s.
Krenzlin H, Lorenz V, Danckwardt S, Kempski O, Alessandri B. The Importance of Thrombin in Cerebral Injury and Disease. Int J Mol Sci [Internet]. 2016[cited 2019 Jan 12];17(1):E84. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730327/pdf/ijms-17-00084.pdf doi: 10.3390/ijms17010084
Sokolova E, Reiser G. Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: Localization, expression and participation in neurodegenerative diseases. Thromb Haemost. 2008;100(4):576–81. doi: 10.1160/TH08-03-0131
Bushi D, Stein ES, Golderman V, Feingold E, Gera O, Chapman J, et al. A Linear Temporal Increase in Thrombin Activity and Loss of Its Receptor in Mouse Brain following Ischemic Stroke. Front Neurol [Internet]. 2017[cited 2019 Jan 12];8:138. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385331/pdf/fneur-08-00138.pdf doi: 10.3389/fneur.2017.00138
Bushi D, Ben Shimon M, Shavit Stein E, Chapman J, Maggio N, Tanne D. Increased thrombin activity following reperfusion after ischemic stroke alters synaptic transmission in the hippocampus. J Neurochem. 2015;135(6):1140-8. doi: 10.1111/jnc.13372
Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann KG, Reiser G. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations. Proc Natl Acad Sci USA. 2000;97(5):2264–9. doi: 10.1073/pnas.040552897
Bao X, Hua Y, Keep RF, Xi G. Thrombin-induced tolerance against oxygen-glucose deprivation in astrocytes: role of protease-activated receptor-1. Cond Med. 2018;1(2):57-63.
Mirante O, Price M, Puentes W, Castillo X, Benakis C, Thevenet J, et al. Endogenous protease nexin-1 protects against cerebral ischemia. Int J Mol Sci. 2013;14(8):16719–31. doi: 10.3390/ijms140816719
Krämer TJ, Sakas W, Jussen D, Krenzlin H, Kempski O, Alessandri B. Thrombin contributes to the injury development and neurological deficit after acute subdural hemorrhage in rats only in collaboration with additional blood-derived factors. BMC Neurosci [Internet]. 2018[cited 2019 Jan 21];19(1):81. Available from: https://bmcneurosci.biomedcentral.com/track/pdf/10.1186/s12868-018-0481-5 doi: 10.1186/s12868-018-0481-5
Wu X, Zhang W, Li JY, Chai BX, Peng J, Wang H, et al. Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus. Neurogastroenterol Motil. 2011;23(3):279–85. doi: 10.1111/j.1365-2982.2010.01641.x
Pleşeru AM, Mihailă RG. The role of thrombin in central nervous system activity and stroke. Clujul Med. 2018;91(4):368–71. doi: 10.15386/cjmed-973
Chen B. Thrombin in Ischemic Stroke Targeting. In: Lapchak PA, Zhang JH, editors. Translational Stroke Research: From Target Selection to Clinical Trials. New York: Springer; 2012, р. 189–204.
Madan R, Gupt B, Saluja S, Kansra UC, Tripathi BK, Guliani BP. Coagulation profile in diabetes and its association with diabetic microvascular complications. J Assoc Physicians India. 2010;58:481-4.
Alzahrani SH, Ajjan RA. Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res. 2010;7(4):260-73. doi: 10.1177/1479164110383723
How to Cite
Copyright (c) 2021 S. Tkachuk, M. Povar, N. Gerush, O. Tkachuk
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Number of views and downloads: 109
Number of citations: 0