Despite obvious progress in the treatment of acute forms of ischemic stroke, the risk of this condition remains unacceptably high. Brain infarction in the middle cerebral artery basin occurs in patients with atherosclerosis. The onset of the brain infarction is facilitated by the cessation of circulation (embolism) in conditions of insufficient collateral circulation. The extent of the infarct zone is determined by neuronal death and impaired microcirculation. The development of new methods for effective targeted restorative stroke therapy is crucial for restorative treatment and reducing the risk of mortality after stroke. Remote ischemic conditioning (RIC) is an approach to limiting reperfusion injury in the ischemic region of the brain after focal ischemia. One of the most commonly used in vivo models in stroke studies is the filament model of Middle Cerebral Artery Occlusion (MCAO) in rats. In our experiment, it was performed for 30 min (J. Koizumi) with subsequent 48-hour reperfusion. Within the first 24 hours after the start of reperfusion several short episodes of ischemia in low limbs were induced. After 48 hours of reperfusion the brains were harvested and stained with TTC. Then we evaluated the effect of RIC within 24 hours ex vivo in rats’ brains, as well as syndecan-1 plasma concentration. Infarct area was assessed by means of Image-Pro program with statistical analysis. Infarct volumes in the model group (31.97% ± 2.5%) were significantly higher compared to the values in the RIC group 48 hours after ischemia-reperfusion (13.6% ± 1.3%) (*P < 0.05). A significant reduction in the area of infarction after RIC is likely due to the effect on the regulation of collateral blood flow in the ischemia area. On the second day after ischemia-reperfusion, tissue swelling was reduced in the RIC group compared to the model group. Analysis of the average concentration of Syndecan-1 revealed the difference between model and RIC groups. Syndecan-1, endothelial glycocalyx protein, might be the regulator which performs vascular control of the interaction with inflammatory cell and is responsible for mediate effect of remote ischemic conditioning on the restriction of ischemic-reperfusion injury.
Ginsberg, M.D. (2016) Expanding the Concept of Neuroprotection for Acute Ischemic Stroke: The Pivotal Roles of Reperfusion and the Collateral Circulation. Progress in Neurobiology, 145-146, 46-77. https://doi.org/10.1016/j.pneurobio.2016.09.002
Zhang, Y., Ma, L., Ren, C., Liu, K., Tian, X., Wu, D., Ding, Y., Li, J., Borlongan, C. V. and Ji, X. (2019) Immediate Remote Ischemic Postconditioning Reduces Cerebral Damage in Ischemic Stroke Mice by Enhancing Leptomeningeal Collateral Circulation. Journal of Cellular Physiology, 234, 12637-12645. https://doi.org/10.1002/jcp.27858
Sommer, C. J. (2017) Ischemic Stroke: Experimental Models and Reality. Acta Neuropathologica, 133, 245-261. https://doi.org/10.1007/s00401-017-1667-0
Kleinschnitz, C., Fluri, F. and Schuhmann, M. (2015) Animal Models of Ischemic Stroke and Their Application in Clinical Research. Drug Design, Development and Therapy, 9, 3445-3454. https://doi.org/10.2147/DDDT.S56071
Koizumi, J. (1986) Experimental Studies of Ischemic Brain Edema. A New Experimental Model of Cerebral Embolism in Rats in Which Recirculation Can Be Introduced in the Ischemic Area. Japanese Journal of Stroke, 8, 1-8. https://doi.org/10.3995/jstroke.8.1
Drunalini Perera, P. N., Hu, Q., Tang, J., Li, L., Barnhart, M., Doycheva, D. M., Zhang, J. H. and Tang, J. (2014) Delayed Remote Ischemic Postconditioning Improves Long Term Sensory Motor Deficits in a Neonatal Hypoxic Ischemic Rat Model. PLoS ONE, 9, e90258. https://doi.org/10.1371/journal.pone.0090258
Sun, J., Li, T., Luan, Q., Deng, J., Li, Y., Li, Z., Dong, H. and Xiong, L. (2012) Protective Effect of Delayed Remote Limb Ischemic Postconditioning: Role of Mitochondrial KATP Channels in a Rat Model of Focal Cerebral Ischemic Reperfusion Injury. Journal of Cerebral Blood Flow & Metabolism, 32, 851-859. https://doi.org/10.1038%2Fjcbfm.2011.199
Ren, C., Yan, Z., Wei, D., Gao, X., Chen, X. and Zhao, H. (2009) Limb Remote Ischemic Postconditioning Protects against Focal Ischemia in Rats. Brain Research, 1288, 88-94. https://doi.org/10.1016/j.brainres.2009.07.029
Qi, W., Zhou, F., Li, S., Zong, Y., Zhang, M., Lin, Y., Zhang, X., Yang, H., Zou, Y., Qi, C., Wang, T. and Hu, X. (2016) Remote Ischemic Postconditioning Protects Ischemic Brain from Injury in Rats with Focal Cerebral Ischemia/Reperfusion Associated with Suppression of TLR4 and NF-кB Expression. NeuroReport, 27, 469-475. https://doi.org/10.1097/WNR.0000000000000553
Lee, J.-S., Song, D.-J., Hong, J.-H., Kim, T.-S. and Joo, S.-P. (2018) Diverse Ischemic Postconditioning Protocols Affect the Infarction Size in Focal Ischemic Stroke. Journal of Cerebrovascular and Endovascular Neurosurgery, 20, 159-167. https://doi.org/10.7461/jcen.2018.20.3.159
Middle Cerebral Artery Occlusion (MCAO)
Remote Ischemic Conditioning (RIC)
Huang, D., Liu, H., Qu, Y. and Wang, P. (2017) Non-Invasive Remote Ischemic Postconditioning Stimulates Neurogenesis during the Recovery Phase after Cerebral Ischemia. Metabolic Brain Disease, 32, 1805-1818. https://doi.org/10.1007/s11011-017-0068-3
Candilio, L., Malik, A. and Hausenloy, D.J. (2013) Protection of Organs Other than the Heart by Remote Ischemic Conditioning. Journal of Cardiovascular Medicine, 14, 193-205. https://doi.org/10.2459/JCM.0b013e328359dd7b
Chen, G., Thakkar, M., Robinson, C. and Doré, S. (2018) Limb Remote Ischemic Conditioning: Mechanisms, Anesthetics, and the Potential for Expanding Therapeutic Options. Frontiers in Neurology, 9, Article No. 40. https://doi.org/10.3389/fneur.2018.00040
Zhao, W., Li, S., Ren, C., Meng, R., Jin, K. and Ji, X. (2019) Remote Ischemic Conditioning for Stroke: Clinical Data, Challenges, and Future Directions. Annals of Clinical and Translational Neurology, 6, 186-196. https://doi.org/10.1002/acn3.691
Garcia, J. H., Wagner, S., Liu, K.-F. and Hu, X. (1995) Neurological Deficit and Extent of Neuronal Necrosis Attributable to Middle Cerebral Artery Occlusion in Rats. Stroke, 26, 627-635. https://doi.org/10.1161/01.STR.26.4.627
Swanson, R.A., Morton, M.T., Tsao-Wu, G., Savalos, R.A., Davidson, C. and Sharp, F.R. (1990) A Semiautomated Method for Measuring Brain Infarct Volume. Journal of Cerebral Blood Flow & Metabolism, 10, 290-293. https://doi.org/10.1038%2Fjcbfm.1990.47
Lee, S. and Lee, D.K. (2018) What Is the Proper Way to Apply the Multiple Comparison Test? Korean Journal of Anesthesiology, 71, 353-360. https://doi.org/10.4097/kja.d.18.00242
McClanahan, T. (1993) Brief Renal Occlusion and Reperfusion Reduces Myocardial Infarct size in Rabbits. FASEB Journal, 7, A118.
Heusch, G., Bøtker, H.E., Przyklenk, K., Redington, A. and Yellon, D. (2015) Remote Ischemic Conditioning. Journal of the American College of Cardiology, 65, 177-195. https://doi.org/10.1016/j.jacc.2014.10.031
Przyklenk, K. and Whittaker, P. (2000) Brief Antecedent Ischemia Enhances Recombinant Tissue Plasminogen Activator-Induced Coronary Thrombolysis by Adenosine-Mediated Mechanism. Circulation, 102, 88-95. https://doi.org/10.1161/01.CIR.102.1.88
Abassi, Z., Armaly, Z. and Heyman, S.N. (2020) Glycocalyx Degradation in Ischemia-Reperfusion Injury. The American Journal of Pathology, 190, 752-767. https://doi.org/10.1016/j.ajpath.2019.08.019
Giacinto, O., Satriano, U., Nenna, A., Spadaccio, C., Lusini, M., Mastroianni, C., Nappi, F. and Chello, M. (2019) Inflammatory Response and Endothelial Dysfunction Following Cardiopulmonary Bypass: Pathophysiology and Pharmacological Targets. Recent Patents on Inflammation & Allergy Drug Discovery, 13, 158-173. https://doi.org/10.2174/1872213X13666190724112644
Chappell, D., Brettner, F., Doerfler, N., Jacob, M., Rehm, M., Bruegger, D., Conzen, P., Jacob, B. and Becker, B. F. (2014) Protection of Glycocalyx Decreases Platelet Adhesion after Ischaemia/Reperfusion. European Journal of Anaesthesiology, 31, 474-481. https://doi.org/10.1097/EJA.0000000000000085
Rabelink, T.J., de Boer, H.C. and van Zonneveld, A.J. (2010) Endothelial Activation and Circulating Markers of Endothelial Activation in Kidney Disease. Nature Reviews Nephrology, 6, 404-414. https://doi.org/10.1038/nrneph.2010.65
Alfieri, R., Vassalli, M. and Viti, F. (2019) Flow-Induced Mechanotransduction in Skeletal Cells. Biophysical Reviews, 11, 729-743.
Zhou, J., Li, Y.-S. and Chien, S. (2014) Shear Stress-Initiated Signaling and Its Regulation of Endothelial Function. Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 2191-2198. https://doi.org/10.1161/ATVBAHA.114.303422
Gonzalez, E., Moore, E.E., Moore, H.B., Theresa, C., Chapman, M., Ghasabyan, A., Silliman, C., Banerjee, A. and Moore, E.E. (2014) Syndecan-1 a Marker of Endothelial Injury Is Associated with Increased Blood Product Requirement and Poor Outcomes in Trauma Patients. Journal of Surgical Research, 186, 588-589. https://doi.org/10.1016/j.jss.2013.11.538
Gonzalez Rodriguez, E., Ostrowski, S.R., Cardenas, J.C., Baer, L.A., Tomasek, J.S., Henriksen, H.H., Stensballe, J., Cotton, B.A., Holcomb, J.B., Johansson, P.I. and Wade, C.E. (2017) Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. Journal of the American College of Surgeons, 225, 419-427. https://doi.org/10.1016/j.jamcollsurg.2017.05.012
Rehm, M., Bruegger, D., Christ, F., Conzen, P., Thiel, M., Jacob, M., Chappell, D., Stoeckelhuber, M., Welsch, U., Reichart, B., Peter, K. and Becker, B.F. (2007) Shedding of the Endothelial Glycocalyx in Patients Undergoing Major Vascular Surgery With Global and Regional Ischemia. Circulation, 116, 1896-1906. https://doi.org/10.1161/CIRCULATIONAHA.106.684852