Volume 26, Issue 5 (10-2022)                   IBJ 2022, 26(5): 357-365 | Back to browse issues page

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Mostafavi H, Amoli N, Ghasemloo E, Forouzandeh M, Hosseini M, Eskandari M. Upregulation of MiRNA-149-5p Reduces the Infract Volume in Middle Cerebral Artery Occlusion Rats by Modulating Cation-Chloride Cotransporters Expressions. IBJ 2022; 26 (5) :357-365
URL: http://ibj.pasteur.ac.ir/article-1-3759-en.html
Introduction: Brain ischemia often leads to the chloride gradient alternations, which affects volume regulation and neuronal survival. Increase in NKCC1 expression and reduction in KCC2 level under ischemic condition results in inflammation and neuronal death. In this study, we investigated the effect of mimic miRNA and CoQ10 on the expression of CCCs (NKCC1 and KCC2) after cerebral ischemia.
Methods: In this study, cerebral ischemia was modeled using the MCAO method. Rats were randomly divided into six groups: sham, model, NC, vehicle, and the first and second treatments. In the Sham group, ischemia was not induced, and no treatment was performed. In the Model group, ischemia induction was performed, and other groups, in addition to ischemia induction, received Scramble miRNA, Ethanol, mimic miRNA-149-5p and CoQ10, respectively. Each group was divided into three subgroups to assess the volume of the tissue damage and NDS in subgroup 1, brain water content in subgroup 2, level of miRNA-149-5p and CCC expressions in subgroup 3.
Results: Our data suggested that the use of mimic miRNA and Q10 increased the level of miRNA-149 and KCC2 expression and decreased NDS, NKCC1 expression, brain water content, and infract volume.
Conclusion: Findings of this study suggest that the mimic miRNA and Q10 may have neuroprotective effects through reducing infract volume and brain water content and modulating the expression of CCCS after brain ischemia.
Type of Study: Full Length | Subject: Medical Biotechnology

1. Eyileten C, Wicik Z, Rosa SD, Mirowska-Guzel D, Soplinska A, Indolfi C, Justrzebska-Kurkowska I, Czlonkowska A, Postula M. MicroRNAs as diagnostic and prognostic biomarkers in ischemic stroke-a comprehensive review and bioinformatic analysis. Cells 2018; 7(12): 249-259. [DOI:10.3390/cells7120249]
2. Zagrean AM, Grigoras IF, Lesanu ML, Lonescu RB, Chitimus DM, Haret RM, Lanosi B, Ceanga M, Zagrean L. Neuronal transmembrane chloride transport has a time-dependent influence on survival of hippocampal cultures to oxygen-glucose deprivation. Brain sciences 2019; 9(12): 360. [DOI:10.3390/brainsci9120360]
3. Liu R, Wang J, Lian S, Zhang g, Yang Z. Role of NKCC1 and KCC2 in epilepsy: from expression to function. Frontiers in neurology 2020; 10:1407. [DOI:10.3389/fneur.2019.01407]
4. He Y, Yu D, Zhu L, Zhing S, Zhao J, Tang J. miR-149 in human cancer: a systemic review. Journal of cancer 2019; 9(2): 375. [DOI:10.7150/jca.21044]
5. Lee YC, Kao ST, Cheng CY. Acorus tatarinowii Schott extract reduces cerebral edema caused by ischemia-reperfusion injury in rats: involvement in regulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated signaling. BMC complementary medicine and therapies 2020; 20(1): 1-17. [DOI:10.1186/s12906-020-03168-z]
6. Wan Y, Jin HU, Zhu YY, Fang Z, Mao L, He Q, Xia YP, Li M, Li Y, Chen X, Hu B. MicroRNA-149-5p regulates blood-brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes. The FASEB journal 2018; 32(6): 3133-3148. [DOI:10.1096/fj.201701121R]
7. Neyrinck AM, Catry E, Sohet FM, Cani PD, Pachikian BD, Bindels LB, Delzenne NM. Lack of anti-inflammatory effect of coenzyme Q10 supplementation in the liver of rodents after lipopolysaccharide challenge. Clinical nutrition experimental 2015; 1: 10-18. [DOI:10.1016/j.yclnex.2015.07.002]
8. Kahle KT, Staley KJ, Nahed BV, Gamba G, Hebert SC, Lifton RP, Mount DB. Roles of the cation-chloride cotransporters in neurological disease. Nature clinical practice neurology 2008; 4(9): 490-503. [DOI:10.1038/ncpneuro0883]
9. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Journal of stroke 1989; 20(1): 84-91. [DOI:10.1161/01.STR.20.1.84]
10. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H . Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986; 17(3): 472-476. [DOI:10.1161/01.STR.17.3.472]
11. Ghasemloo E, Oryan S, Reza M, Hossein B, Mehdi M, Eskandari. The neuroprotective efect of microRNA-149-5p and coenzymeQ10 by reducing levels of infammatory cytokines and metalloproteinases following focal brain ischemia in rats. Brain research bulletin 2021; 169: 205-213. [DOI:10.1016/j.brainresbull.2021.01.013]
12. Ghasemloo E, Mostafavi H, Hosseini M, Forouzandeh M, Eskandari M, Mousavi SS. Neuroprotective efects of coenzyme Q10 in Parkinson's model via a novel Q10/miR-149-5p/MMPs pathway. Metabolic brain disease 2021b; 36(7): 2089-2100. [DOI:10.1007/s11011-021-00795-4]
13. Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Doring F. Functions of coenzyme Q10 in inflammation and gene expression. BioFactors 2008; 32(1-4): 179-183. [DOI:10.1002/biof.5520320121]
14. Ambros V . The functions of animal microRNAs. Nature 2004; 431(7006): 350-355. [DOI:10.1038/nature02871]
15. Wang D, Yan X, Xia M, Yang Y, Li D, Li X, Song F, Ling W. Coenzyme Q10 Promotes macrophage cholesterol efflux by regulation of the activator protein-1/miR-378/ATP-binding cassette transporter G1-signaling pathway. Arteriosclerosis, thrombosis, and vascular biology 2014; 34(9): 1861-1870. [DOI:10.1161/ATVBAHA.113.302879]
16. Chen H, Sun D. The role of Na-K-Cl co-transporter in cerebral ischemia. Neurological research 2005; 27(3): 280-286. [DOI:10.1179/016164105X25243]
17. Yan Y, Dempsey RJ, Flemmer A, Forbush B, Sun D. Inhibition of Na+-K+-Cl− cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain research 2003; 961(1): 22-31. [DOI:10.1016/S0006-8993(02)03832-5]
18. Bhuiyan MIH, Song S, Yuan H, Begum G, Kofler J, Kahle KT, Yang SS, Lin SH, Alper SL, Subramanya AR. WNK-Cab39-NKCC1 signaling increases the susceptibility to ischemic brain damage in hypertensive rats. Journal of cerebral blood flow and metabolism 2017; 37(8): 2780-2794. [DOI:10.1177/0271678X16675368]
19. Huang H, Bhuiyan MIH, Jiang T, Song S, Shankar S, Taheri T, Li E, Schreppel P, Hintersteininger M, Yang SS, Lin SH, Molyneaux BJ, Zhang Z, Erker T, Sun D. A novel Na+-K+-Cl− cotransporter 1 inhibitor STS66* reduces brain damage in mice after ischemic stroke. Stroke 2019; 50(4): 1021-1025. [DOI:10.1161/STROKEAHA.118.024287]
20. Jing L, He MT, Chang Y, Mehta SL, He QP, Zhang JZ, Li PA. Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway. International journal of biological sciences 2015; 11(1): 59. [DOI:10.7150/ijbs.10174]
21. Belousova M, Tokareva O, Gorodetskaya E, Kalenikova EI, Medvedev OS. Intravenous treatment with coenzyme Q10 improves neurological outcome and reduces infarct volume after transient focal brain ischemia in rats. Journal of cardiovascular pharmacology 2016; 67(2): 103-109. [DOI:10.1097/FJC.0000000000000320]
22. Pedersen SF, Donnell ME, Anderson SE, Cala PM. Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood. American journal of physiology. regulatory, integrative and comparative physiology. 2006; 291(1): R1-R25. [DOI:10.1152/ajpregu.00782.2005]
23. Lippi G, Fernandes CC, Ewell LA, John D, Romoli B, Guria g, Taylor SA, Frady EP, Jensen AB, Liu JC, Chaabane MM, Belal C, Nathanson JL, Zoli M, Liutgeb JK, Biagini G, Yeo GW, Berg DK. MicroRNA-101 regulates multiple developmental programs to constrain excitation in adult neural networks. Neuron 2016; 92(2): 1337-1351. [DOI:10.1016/j.neuron.2016.11.017]
24. Chen L, Wan L, Wu Z, Ren W, Huang Y, Qian B, Wang Y. KCC2 downregulation facilitates epileptic seizures. Scientific reports 2017; 7(1): 1-13. [DOI:10.1038/s41598-017-00196-7]
25. Raol YH, Joksimovic SM, Sampath D, Matter BA, Lam PM, Kompella UB, Todorovic SM, Gozalaze MI. The role of KCC2 in hyperexcitability of the neonatal brain. Neuroscience letters 2020; 738: 135324. [DOI:10.1016/j.neulet.2020.135324]
26. Xie L, Xie Y, Mao G, Cao S, Fang R, Zhou S, Jiang J, Yao T, Fan J, Liu D, Wu D, Ge J. Decreased spasticity of Baishaoluoshi Decoction through the BDNF/TrKB-KCC2 pathway on poststroke spasticity rats. Neuroreport 2021; 32(14): 1183. [DOI:10.1097/WNR.0000000000001709]
27. Yang CY, Liu SY, Wang HY, Li Y, Guo D, Wang X, Hua W, Wang G. Neuroprotection by propofol post-conditioning: focus on PKMζ/KCC2 pathway activity. Cellular and molecular neurobiology 2018; 38: 691-701. [DOI:10.1007/s10571-017-0530-0]
28. Wan Y, Jin HU, Zhu YY, Fang Z, Mao L, He Q, Xia YP, Li M, Li Y, Chen X, Hu B. MicroRNA-149-5p regulates blood-brain barrier permeability after transient middle cerebral artery occlusion in rats by targeting S1PR2 of pericytes. The FASEB journal 2018; 32(6): 3133-3148. [DOI:10.1096/fj.201701121R]
29. Teertam SK, Jha S, Babu PP. Up-regulation of Sirt1/miR-149-5p signaling may play a role in resveratrol induced protection against ischemia via p53 in rat brain. Journal of clinical neuroscience 2020; 72: 402-411. [DOI:10.1016/j.jocn.2019.11.043]
30. Obolenskaia ON, Gorodetskaya EA, Kalenikova EI, Belousova MA, Gulyaev MN, Makarov VG, Pirogov YA, Medvedev OS. Intravenous administration of coenzyme Q10 in acute period of cerebral ischemia decreases mortality by reducing brain necrosis and limiting its increase within 4 days in rat stroke model. Antioxidants 2020; 9(12): 1240. [DOI:10.3390/antiox9121240]
31. Nasoohi S, Simani L, Khodegholi F, Nikseresht S, Faizi M, Naderi N . Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin. Nutritional neuroscience 2019; 22(4): 264-272. [DOI:10.1080/1028415X.2017.1376928]

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