Generic placeholder image

Current Neuropharmacology

Author(s): Guofang Shen and Qingyi Ma*

DOI: 10.2174/1570159X18666200429004242

DownloadDownload PDF Flyer Cite As
MicroRNAs in the Blood-Brain Barrier in Hypoxic-Ischemic Brain Injury

Page: [1180 - 1186] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Hypoxic-ischemic (HI) brain injury is a leading cause of acute mortality and chronic disability in newborns. Current evidence shows that cerebral microvascular response and compromised blood-brain barrier (BBB) integrity occur rapidly and could primarily be responsible for the brain injury observed in many infants with HI brain injury. MicroRNAs (miRNAs) are a type of highly conserved non-coding RNAs (ncRNAs), which consist of 21-25 nucleotides in length and usually lead to suppression of target gene expression. Growing evidence has revealed that brainenriched miRNAs act as versatile regulators of BBB dysfunctions in various neurological disorders including neonatal HI brain injury. In the present review, we summarize the current findings regarding the role of miRNAs in BBB impairment after hypoxia/ischemia brain injury. Specifically, we focus on the recent progress of miRNAs in the pathologies of neonatal HI brain injury. These findings can not only deepen our understanding of the role of miRNAs in BBB impairment in HI brain injury, but also provide insight into the development of new therapeutic strategies for preservation of BBB integrity under pathological conditions.

Keywords: Hypoxic ischemia encephalopathy (HIE), ischemic stroke, miRNA, BBB disruption, MMP, tight junction, neural inflammation.

Graphical Abstract

[1]
Molloy, E.J.; Bearer, C. Neonatal encephalopathy versus Hypoxic-Ischemic Encephalopathy. Pediatr. Res., 2018, 84(5), 574.
[http://dx.doi.org/10.1038/s41390-018-0169-7] [PMID: 30214023]
[2]
Kurinczuk, J.J.; White-Koning, M.; Badawi, N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum. Dev., 2010, 86(6), 329-338.
[http://dx.doi.org/10.1016/j.earlhumdev.2010.05.010] [PMID: 20554402]
[3]
Allen, K.A.; Brandon, D.H. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments. Newborn Infant Nurs. Rev., 2011, 11(3), 125-133.
[http://dx.doi.org/10.1053/j.nainr.2011.07.004] [PMID: 21927583]
[4]
Douglas-Escobar, M.; Weiss, M.D. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr., 2015, 169(4), 397-403.
[http://dx.doi.org/10.1001/jamapediatrics.2014.3269] [PMID: 25685948]
[5]
Stamatovic, S.M.; Phillips, C.M.; Martinez-Revollar, G.; Keep, R.F.; Andjelkovic, A.V. Involvement of Epigenetic Mechanisms and Non-coding RNAs in Blood-Brain Barrier and Neurovascular Unit Injury and Recovery After Stroke. Front. Neurosci., 2019, 13, 864.
[http://dx.doi.org/10.3389/fnins.2019.00864] [PMID: 31543756]
[6]
Vasiljevic, B.; Maglajlic-Djukic, S.; Gojnic, M.; Stankovic, S.; Ignjatovic, S.; Lutovac, D. New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury. Pediatr. Int., 2011, 53(4), 454-462.
[http://dx.doi.org/10.1111/j.1442-200X.2010.03290.x] [PMID: 21077993]
[7]
Ek, C.J.; D’Angelo, B.; Baburamani, A.A.; Lehner, C.; Leverin, A.L.; Smith, P.L.; Nilsson, H.; Svedin, P.; Hagberg, H.; Mallard, C. Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia. J. Cereb. Blood Flow Metab., 2015, 35(5), 818-827.
[http://dx.doi.org/10.1038/jcbfm.2014.255] [PMID: 25627141]
[8]
Chen, X.; Threlkeld, S.W.; Cummings, E.E.; Juan, I.; Makeyev, O.; Besio, W.G.; Gaitanis, J.; Banks, W.A.; Sadowska, G.B.; Stonestreet, B.S. Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus. Neuroscience, 2012, 226, 89-100.
[http://dx.doi.org/10.1016/j.neuroscience.2012.08.043] [PMID: 22986172]
[9]
Ferrari, D.C.; Nesic, O.B.; Perez-Polo, J.R. Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edema. J. Neurosci. Res., 2010, 88(9), 2056-2065.
[http://dx.doi.org/10.1002/jnr.22358] [PMID: 20143414]
[10]
Benjelloun, N.; Renolleau, S.; Represa, A.; Ben-Ari, Y.; Charriaut-Marlangue, C. Inflammatory responses in the cerebral cortex after ischemia in the P7 neonatal Rat. Stroke, 1999, 30(9), 1916-1923.
[http://dx.doi.org/10.1161/01.STR.30.9.1916] [PMID: 10471445]
[11]
Kumar, A.; Mittal, R.; Khanna, H.D.; Basu, S. Free radical injury and blood-brain barrier permeability in hypoxic-ischemic encephalopathy. Pediatrics, 2008, 122(3), e722-e727.
[http://dx.doi.org/10.1542/peds.2008-0269] [PMID: 18725389]
[12]
Moretti, R.; Pansiot, J.; Bettati, D.; Strazielle, N.; Ghersi-Egea, J.F.; Damante, G.; Fleiss, B.; Titomanlio, L.; Gressens, P. Blood-brain barrier dysfunction in disorders of the developing brain. Front. Neurosci., 2015, 9, 40.
[http://dx.doi.org/10.3389/fnins.2015.00040] [PMID: 25741233]
[13]
Ma, Q.; Zhang, L.; Pearce, W.J. MicroRNAs in brain development and cerebrovascular pathophysiology. Am. J. Physiol. Cell Physiol., 2019, 317(1), C3-C19.
[http://dx.doi.org/10.1152/ajpcell.00022.2019] [PMID: 30840494]
[14]
Inui, M.; Martello, G.; Piccolo, S. MicroRNA control of signal transduction. Nat. Rev. Mol. Cell Biol., 2010, 11(4), 252-263.
[http://dx.doi.org/10.1038/nrm2868] [PMID: 20216554]
[15]
Sun, W.; Julie Li, Y.S.; Huang, H.D.; Shyy, J.Y.; Chien, S. microRNA: a master regulator of cellular processes for bioengineering systems. Annu. Rev. Biomed. Eng., 2010, 12, 1-27.
[http://dx.doi.org/10.1146/annurev-bioeng-070909-105314] [PMID: 20415587]
[16]
Ponnusamy, V.; Yip, P.K. The role of microRNAs in newborn brain development and hypoxic ischaemic encephalopathy. Neuropharmacology, 2019, 149, 55-65.
[http://dx.doi.org/10.1016/j.neuropharm.2018.11.041] [PMID: 30716413]
[17]
Rink, C.; Khanna, S. MicroRNA in ischemic stroke etiology and pathology. Physiol. Genomics, 2011, 43(10), 521-528.
[http://dx.doi.org/10.1152/physiolgenomics.00158.2010] [PMID: 20841499]
[18]
Rosenberg, G.A. Ischemic brain edema. Prog. Cardiovasc. Dis., 1999, 42(3), 209-216.
[http://dx.doi.org/10.1016/S0033-0620(99)70003-4] [PMID: 10598921]
[19]
Yao, Y. Basement membrane and stroke. J. Cereb. Blood Flow Metab., 2019, 39(1), 3-19.
[http://dx.doi.org/10.1177/0271678X18801467] [PMID: 30226080]
[20]
Ballabh, P.; Braun, A.; Nedergaard, M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol. Dis., 2004, 16(1), 1-13.
[http://dx.doi.org/10.1016/j.nbd.2003.12.016] [PMID: 15207256]
[21]
Hawkins, B.T.; Davis, T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev., 2005, 57(2), 173-185.
[http://dx.doi.org/10.1124/pr.57.2.4] [PMID: 15914466]
[22]
Brown, L.S.; Foster, C.G.; Courtney, J.M.; King, N.E.; Howells, D.W.; Sutherland, B.A. Pericytes and Neurovascular Function in the Healthy and Diseased Brain. Front. Cell. Neurosci., 2019, 13, 282.
[http://dx.doi.org/10.3389/fncel.2019.00282] [PMID: 31316352]
[23]
Campbell, H.K.; Maiers, J.L.; DeMali, K.A. Interplay between tight junctions & adherens junctions. Exp. Cell Res., 2017, 358(1), 39-44.
[http://dx.doi.org/10.1016/j.yexcr.2017.03.061] [PMID: 28372972]
[24]
Stamatovic, S.M.; Keep, R.F.; Andjelkovic, A.V. Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr. Neuropharmacol., 2008, 6(3), 179-192.
[http://dx.doi.org/10.2174/157015908785777210] [PMID: 19506719]
[25]
Anderson, J.M.; Van Itallie, C.M. Physiology and function of the tight junction. Cold Spring Harb. Perspect. Biol., 2009, 1(2)a002584
[http://dx.doi.org/10.1101/cshperspect.a002584] [PMID: 20066090]
[26]
Ek, C.J.; Dziegielewska, K.M.; Habgood, M.D.; Saunders, N.R. Barriers in the developing brain and Neurotoxicology. Neurotoxicology, 2012, 33(3), 586-604.
[http://dx.doi.org/10.1016/j.neuro.2011.12.009] [PMID: 22198708]
[27]
Saunders, N.R.; Liddelow, S.A.; Dziegielewska, K.M. Barrier mechanisms in the developing brain. Front. Pharmacol., 2012, 3, 46.
[http://dx.doi.org/10.3389/fphar.2012.00046] [PMID: 22479246]
[28]
Mallard, C.; Ek, C.J.; Vexler, Z.S. The myth of the immature barrier systems in the developing brain: role in perinatal brain injury. J. Physiol., 2018, 596(23), 5655-5664.
[http://dx.doi.org/10.1113/JP274938] [PMID: 29528501]
[29]
Reemst, K.; Noctor, S.C.; Lucassen, P.J.; Hol, E.M. The Indispensable Roles of Microglia and Astrocytes during Brain Development. Front. Hum. Neurosci., 2016, 10, 566.
[http://dx.doi.org/10.3389/fnhum.2016.00566] [PMID: 27877121]
[30]
Haddad-Tóvolli, R.; Dragano, N.R.V.; Ramalho, A.F.S.; Velloso, L.A. Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control. Front. Neurosci., 2017, 11, 224.
[http://dx.doi.org/10.3389/fnins.2017.00224] [PMID: 28484368]
[31]
Jiang, X.; Andjelkovic, A.V.; Zhu, L.; Yang, T.; Bennett, M.V.L.; Chen, J.; Keep, R.F.; Shi, Y. Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog. Neurobiol., 2018, 163-164, 144-171.
[http://dx.doi.org/10.1016/j.pneurobio.2017.10.001] [PMID: 28987927]
[32]
Ma, F.; Zhang, X.; Yin, K.J. MicroRNAs in central nervous system diseases: A prospective role in regulating blood-brain barrier integrity. Exp. Neurol., 2020, 323113094
[http://dx.doi.org/10.1016/j.expneurol.2019.113094] [PMID: 31676317]
[33]
Cerutti, C.; Ridley, A.J. Endothelial cell-cell adhesion and signaling. Exp. Cell Res., 2017, 358(1), 31-38.
[http://dx.doi.org/10.1016/j.yexcr.2017.06.003] [PMID: 28602626]
[34]
Shi, Y.; Zhang, L.; Pu, H.; Mao, L.; Hu, X.; Jiang, X.; Xu, N.; Stetler, R.A.; Zhang, F.; Liu, X.; Leak, R.K.; Keep, R.F.; Ji, X.; Chen, J. Rapid endothelial cytoskeletal reorganization enables early blood-brain barrier disruption and long-term ischaemic reperfusion brain injury. Nat. Commun., 2016, 7, 10523.
[http://dx.doi.org/10.1038/ncomms10523] [PMID: 26813496]
[35]
Shi, Y.; Jiang, X.; Zhang, L.; Pu, H.; Hu, X.; Zhang, W.; Cai, W.; Gao, Y.; Leak, R.K.; Keep, R.F.; Bennett, M.V.; Chen, J. Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood-brain barrier disruption after ischemic brain injury. Proc. Natl. Acad. Sci. USA, 2017, 114(7), E1243-E1252.
[http://dx.doi.org/10.1073/pnas.1621174114] [PMID: 28137866]
[36]
Kratzer, I.; Chip, S.; Vexler, Z.S. Barrier mechanisms in neonatal stroke. Front. Neurosci., 2014, 8, 359.
[http://dx.doi.org/10.3389/fnins.2014.00359] [PMID: 25426016]
[37]
Fernández-López, D.; Faustino, J.; Daneman, R.; Zhou, L.; Lee, S.Y.; Derugin, N.; Wendland, M.F.; Vexler, Z.S. Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat. J. Neurosci., 2012, 32(28), 9588-9600.
[http://dx.doi.org/10.1523/JNEUROSCI.5977-11.2012] [PMID: 22787045]
[38]
Ferrari, D.C.; Nesic, O.; Perez-Polo, J.R. Perspectives on neonatal hypoxia/ischemia-induced edema formation. Neurochem. Res., 2010, 35(12), 1957-1965.
[http://dx.doi.org/10.1007/s11064-010-0308-y] [PMID: 21136160]
[39]
Lv, H.; Wang, Q.; Wu, S.; Yang, L.; Ren, P.; Yang, Y.; Gao, J.; Li, L. Neonatal hypoxic ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid. Clin. Chim. Acta, 2015, 450, 282-297.
[http://dx.doi.org/10.1016/j.cca.2015.08.021] [PMID: 26320853]
[40]
Ha, M.; Kim, V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol., 2014, 15(8), 509-524.
[http://dx.doi.org/10.1038/nrm3838] [PMID: 25027649]
[41]
O’Brien, J.; Hayder, H.; Zayed, Y.; Peng, C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol. (Lausanne), 2018, 9, 402.
[http://dx.doi.org/10.3389/fendo.2018.00402] [PMID: 30123182]
[42]
Kreth, S.; Hübner, M.; Hinske, L.C. MicroRNAs as Clinical Biomarkers and Therapeutic Tools in Perioperative Medicine. Anesth. Analg., 2018, 126(2), 670-681.
[http://dx.doi.org/10.1213/ANE.0000000000002444] [PMID: 28922229]
[43]
Chien, C.H.; Sun, Y.M.; Chang, W.C.; Chiang-Hsieh, P.Y.; Lee, T.Y.; Tsai, W.C.; Horng, J.T.; Tsou, A.P.; Huang, H.D. Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data. Nucleic Acids Res., 2011, 39(21), 9345-9356.
[http://dx.doi.org/10.1093/nar/gkr604] [PMID: 21821656]
[44]
Lawrie, C.H.; Gal, S.; Dunlop, H.M.; Pushkaran, B.; Liggins, A.P.; Pulford, K.; Banham, A.H.; Pezzella, F.; Boultwood, J.; Wainscoat, J.S.; Hatton, C.S.; Harris, A.L. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol., 2008, 141(5), 672-675.
[http://dx.doi.org/10.1111/j.1365-2141.2008.07077.x] [PMID: 18318758]
[45]
Chim, S.S.; Shing, T.K.; Hung, E.C.; Leung, T.Y.; Lau, T.K.; Chiu, R.W.; Lo, Y.M. Detection and characterization of placental microRNAs in maternal plasma. Clin. Chem., 2008, 54(3), 482-490.
[http://dx.doi.org/10.1373/clinchem.2007.097972] [PMID: 18218722]
[46]
Turchinovich, A.; Weiz, L.; Burwinkel, B. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem. Sci., 2012, 37(11), 460-465.
[http://dx.doi.org/10.1016/j.tibs.2012.08.003] [PMID: 22944280]
[47]
Zernecke, A.; Bidzhekov, K.; Noels, H.; Shagdarsuren, E.; Gan, L.; Denecke, B.; Hristov, M.; Köppel, T.; Jahantigh, M.N.; Lutgens, E.; Wang, S.; Olson, E.N.; Schober, A.; Weber, C. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci. Signal., 2009, 2(100), ra81.
[http://dx.doi.org/10.1126/scisignal.2000610] [PMID: 19996457]
[48]
Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9(6), 654-659.
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[49]
Arroyo, J.D.; Chevillet, J.R.; Kroh, E.M.; Ruf, I.K.; Pritchard, C.C.; Gibson, D.F.; Mitchell, P.S.; Bennett, C.F.; Pogosova-Agadjanyan, E.L.; Stirewalt, D.L.; Tait, J.F.; Tewari, M. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. USA, 2011, 108(12), 5003-5008.
[http://dx.doi.org/10.1073/pnas.1019055108] [PMID: 21383194]
[50]
Turchinovich, A.; Samatov, T.R.; Tonevitsky, A.G.; Burwinkel, B. Circulating miRNAs: cell-cell communication function? Front. Genet., 2013, 4, 119.
[http://dx.doi.org/10.3389/fgene.2013.00119] [PMID: 23825476]
[51]
Zuo, X.; Lu, J.; Manaenko, A.; Qi, X.; Tang, J.; Mei, Q.; Xia, Y.; Hu, Q. MicroRNA-132 attenuates cerebral injury by protecting blood-brain-barrier in MCAO mice. Exp. Neurol., 2019, 316, 12-19.
[http://dx.doi.org/10.1016/j.expneurol.2019.03.017] [PMID: 30930097]
[52]
Fan, F.; Yang, J.; Xu, Y.; Guan, S. MiR-539 Targets MMP-9 to Regulate the Permeability of Blood-Brain Barrier in Ischemia/Reperfusion Injury of Brain. Neurochem. Res., 2018, 43(12), 2260-2267.
[http://dx.doi.org/10.1007/s11064-018-2646-0] [PMID: 30276507]
[53]
Fang, Z.; He, Q.W.; Li, Q.; Chen, X.L.; Baral, S.; Jin, H.J.; Zhu, Y.Y.; Li, M.; Xia, Y.P.; Mao, L.; Hu, B. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. FASEB J., 2016, 30(6), 2097-2107.
[http://dx.doi.org/10.1096/fj.201500126] [PMID: 26887441]
[54]
Gamble, J.R.; Drew, J.; Trezise, L.; Underwood, A.; Parsons, M.; Kasminkas, L.; Rudge, J.; Yancopoulos, G.; Vadas, M.A. Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions. Circ. Res., 2000, 87(7), 603-607.
[http://dx.doi.org/10.1161/01.RES.87.7.603] [PMID: 11009566]
[55]
Milam, K.E.; Parikh, S.M. The angiopoietin-Tie2 signaling axis in the vascular leakage of systemic inflammation. Tissue Barriers, 2015, 3(1-2)e957508
[http://dx.doi.org/10.4161/21688362.2014.957508] [PMID: 25838975]
[56]
Bai, Y.; Zhang, Y.; Han, B.; Yang, L.; Chen, X.; Huang, R.; Wu, F.; Chao, J.; Liu, P.; Hu, G.; Zhang, J.H.; Yao, H. Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood-Brain Barrier Integrity. J. Neurosci., 2018, 38(1), 32-50.
[PMID: 29114076]
[57]
Wang, Y.; Wang, M.D.; Xia, Y.P.; Gao, Y.; Zhu, Y.Y.; Chen, S.C.; Mao, L.; He, Q.W.; Yue, Z.Y.; Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5. FASEB J., 2018, 32(2), 935-944.
[http://dx.doi.org/10.1096/fj.201700139RRR] [PMID: 29070584]
[58]
Pena-Philippides, J.C.; Gardiner, A.S.; Caballero-Garrido, E.; Pan, R.; Zhu, Y.; Roitbak, T. Inhibition of MicroRNA-155 Supports Endothelial Tight Junction Integrity Following Oxygen-Glucose Deprivation. J. Am. Heart Assoc., 2018, 7(13)e009244
[http://dx.doi.org/10.1161/JAHA.118.009244] [PMID: 29945912]
[59]
Bukeirat, M.; Sarkar, S.N.; Hu, H.; Quintana, D.D.; Simpkins, J.W.; Ren, X. MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c. J. Cereb. Blood Flow Metab., 2016, 36(2), 387-392.
[http://dx.doi.org/10.1177/0271678X15606147] [PMID: 26661155]
[60]
Hu, H.; Hone, E.A.; Provencher, E.A.P.; Sprowls, S.A.; Farooqi, I.; Corbin, D.R.; Sarkar, S.N.; Hollander, J.M.; Lockman, P.R.; Simpkins, J.W.; Ren, X. MiR-34a Interacts with Cytochrome c and Shapes Stroke Outcomes. Sci. Rep., 2020, 10(1), 3233.
[http://dx.doi.org/10.1038/s41598-020-59997-y] [PMID: 32094435]
[61]
Li, Z.; Li, J.; Tang, N. Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-26b and upregulating ULK2 expression. Neuroscience, 2017, 354, 1-10.
[http://dx.doi.org/10.1016/j.neuroscience.2017.04.017] [PMID: 28433650]
[62]
Yin, K.J.; Deng, Z.; Hamblin, M.; Xiang, Y.; Huang, H.; Zhang, J.; Jiang, X.; Wang, Y.; Chen, Y.E. Peroxisome proliferator-activated receptor delta regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury. J. Neurosci., 2010, 30(18), 6398-6408.
[http://dx.doi.org/10.1523/JNEUROSCI.0780-10.2010] [PMID: 20445066]
[63]
Wan, Y.; Jin, H.J.; Zhu, Y.Y.; Fang, Z.; Mao, L.; He, Q.; Xia, Y.P.; 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. FASEB J., 2018, 32(6), 3133-3148.
[http://dx.doi.org/10.1096/fj.201701121R] [PMID: 29401609]
[64]
Wang, Y.; Huang, J.; Ma, Y.; Tang, G.; Liu, Y.; Chen, X.; Zhang, Z.; Zeng, L.; Wang, Y.; Ouyang, Y.B.; Yang, G.Y. MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4. J. Cereb. Blood Flow Metab., 2015, 35(12), 1977-1984.
[http://dx.doi.org/10.1038/jcbfm.2015.156] [PMID: 26126866]
[65]
Sepramaniam, S.; Ying, L.K.; Armugam, A.; Wintour, E.M.; Jeyaseelan, K. MicroRNA-130a represses transcriptional activity of aquaporin 4 M1 promoter. J. Biol. Chem., 2012, 287(15), 12006-12015.
[http://dx.doi.org/10.1074/jbc.M111.280701] [PMID: 22334710]
[66]
Sepramaniam, S.; Armugam, A.; Lim, K.Y.; Karolina, D.S.; Swaminathan, P.; Tan, J.R.; Jeyaseelan, K. MicroRNA 320a functions as a novel endogenous modulator of aquaporins 1 and 4 as well as a potential therapeutic target in cerebral ischemia. J. Biol. Chem., 2010, 285(38), 29223-29230.
[http://dx.doi.org/10.1074/jbc.M110.144576] [PMID: 20628061]
[67]
Tang, G.; Yang, G.Y. Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema. Int. J. Mol. Sci., 2016, 17(10)E1413
[http://dx.doi.org/10.3390/ijms17101413] [PMID: 27690011]
[68]
Badaut, J.; Ashwal, S.; Tone, B.; Regli, L.; Tian, H.R.; Obenaus, A. Temporal and regional evolution of aquaporin-4 expression and magnetic resonance imaging in a rat pup model of neonatal stroke. Pediatr. Res., 2007, 62(3), 248-254.
[http://dx.doi.org/10.1203/PDR.0b013e3180db291b] [PMID: 17622964]
[69]
Pan, J.; Qu, M.; Li, Y.; Wang, L.; Zhang, L.; Wang, Y.; Tang, Y.; Tian, H.L.; Zhang, Z.; Yang, G.Y. MicroRNA-126-3p/-5p Overexpression Attenuates Blood-Brain Barrier Disruption in a Mouse Model of Middle Cerebral Artery Occlusion. Stroke, 2020, 51(2), 619-627.
[http://dx.doi.org/10.1161/STROKEAHA.119.027531] [PMID: 31822249]
[70]
Chu, B.; Zhou, Y.; Zhai, H.; Li, L.; Sun, L.; Li, Y. The role of microRNA-146a in regulating the expression of IRAK1 in cerebral ischemia-reperfusion injury. Can. J. Physiol. Pharmacol., 2018, 96(6), 611-617.
[http://dx.doi.org/10.1139/cjpp-2017-0586] [PMID: 29505740]
[71]
Bernstein, D.L.; Zuluaga-Ramirez, V.; Gajghate, S.; Reichenbach, N.L.; Polyak, B.; Persidsky, Y.; Rom, S. miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model. J Cereb Blood Flow Metab 2019. 271678X19882264
[72]
Huang, L.; Ma, Q.; Li, Y.; Li, B.; Zhang, L. Inhibition of microRNA-210 suppresses pro-inflammatory response and reduces acute brain injury of ischemic stroke in mice. Exp. Neurol., 2018, 300, 41-50.
[http://dx.doi.org/10.1016/j.expneurol.2017.10.024] [PMID: 29111308]
[73]
Lopez-Ramirez, M.A.; Wu, D.; Pryce, G.; Simpson, J.E.; Reijerkerk, A.; King-Robson, J.; Kay, O.; de Vries, H.E.; Hirst, M.C.; Sharrack, B.; Baker, D.; Male, D.K.; Michael, G.J.; Romero, I.A. MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. FASEB J., 2014, 28(6), 2551-2565.
[http://dx.doi.org/10.1096/fj.13-248880] [PMID: 24604078]
[74]
Whitehead, C.L.; Teh, W.T.; Walker, S.P.; Leung, C.; Larmour, L.; Tong, S. Circulating MicroRNAs in maternal blood as potential biomarkers for fetal hypoxia in-utero. PLoS One, 2013, 8(11)e78487
[http://dx.doi.org/10.1371/journal.pone.0078487] [PMID: 24282500]
[75]
Ma, Q.; Dasgupta, C.; Li, Y.; Bajwa, N.M.; Xiong, F.; Harding, B.; Hartman, R.; Zhang, L. Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats. Neurobiol. Dis., 2016, 89, 202-212.
[http://dx.doi.org/10.1016/j.nbd.2016.02.011] [PMID: 26875527]
[76]
Chan, Y.C.; Banerjee, J.; Choi, S.Y.; Sen, C.K. miR-210: the master hypoxamir. Microcirculation, 2012, 19(3), 215-223.
[http://dx.doi.org/10.1111/j.1549-8719.2011.00154.x] [PMID: 22171547]
[77]
Zeng, L.; He, X.; Wang, Y.; Tang, Y.; Zheng, C.; Cai, H.; Liu, J.; Wang, Y.; Fu, Y.; Yang, G.Y. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain. Gene Ther., 2014, 21(1), 37-43.
[http://dx.doi.org/10.1038/gt.2013.55] [PMID: 24152581]
[78]
Ma, Q.; Dasgupta, C.; Li, Y.; Huang, L.; Zhang, L. MicroRNA-210 Suppresses Junction Proteins and Disrupts Blood-Brain Barrier Integrity in Neonatal Rat Hypoxic-Ischemic Brain Injury. Int. J. Mol. Sci., 2017, 18(7)E1356
[http://dx.doi.org/10.3390/ijms18071356] [PMID: 28672801]
[79]
Li, Y.; Huang, L.; Ma, Q.; Concepcion, K.R.; Song, M.A.; Zhang, P.; Fu, Y.; Xiao, D.; Zhang, L. Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice. Int. J. Mol. Sci., 2018, 19(8)E2428
[http://dx.doi.org/10.3390/ijms19082428] [PMID: 30126083]
[80]
Li, B.; Dasgupta, C.; Huang, L.; Meng, X.; Zhang, L. MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy. Cell. Mol. Immunol., 2020, 17(9), 976-991.
[http://dx.doi.org/10.1038/s41423-019-0257-6] [PMID: 31300734]
[81]
Jiang, Y.; Li, L.; Tan, X.; Liu, B.; Zhang, Y.; Li, C. miR-210 mediates vagus nerve stimulation-induced antioxidant stress and anti-apoptosis reactions following cerebral ischemia/reperfusion injury in rats. J. Neurochem., 2015, 134(1), 173-181.
[http://dx.doi.org/10.1111/jnc.13097] [PMID: 25783636]
[82]
Meng, Z.Y.; Kang, H.L.; Duan, W.; Zheng, J.; Li, Q.N.; Zhou, Z.J. MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway. J. Am. Heart Assoc., 2018, 7(5)e005052
[http://dx.doi.org/10.1161/JAHA.116.005052] [PMID: 29478968]
[83]
Garberg, H.T.; Huun, M.U.; Baumbusch, L.O.; Åsegg-Atneosen, M.; Solberg, R.; Saugstad, O.D. Temporal Profile of Circulating microRNAs after Global Hypoxia-Ischemia in Newborn Piglets. Neonatology, 2017, 111(2), 133-139.
[http://dx.doi.org/10.1159/000449032] [PMID: 27750254]
[84]
Ge, X.; Han, Z.; Chen, F.; Wang, H.; Zhang, B.; Jiang, R.; Lei, P.; Zhang, J. MiR-21 alleviates secondary blood-brain barrier damage after traumatic brain injury in rats. Brain Res., 2015, 1603, 150-157.
[http://dx.doi.org/10.1016/j.brainres.2015.01.009] [PMID: 25598202]
[85]
Yao, X.; Wang, Y.; Zhang, D. microRNA-21 Confers Neuroprotection Against Cerebral Ischemia-Reperfusion Injury and Alleviates Blood-Brain Barrier Disruption in Rats via the MAPK Signaling Pathway. J. Mol. Neurosci., 2018, 65(1), 43-53.
[http://dx.doi.org/10.1007/s12031-018-1067-5] [PMID: 29696468]
[86]
Cho, K.H.T.; Xu, B.; Blenkiron, C.; Fraser, M. Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury. Front. Physiol., 2019, 10, 227.
[http://dx.doi.org/10.3389/fphys.2019.00227] [PMID: 30984006]
[87]
Zhou, T.; Huang, Y.X.; Song, J.W.; Ma, Q.M. Thymosin β4 inhibits microglia activation through microRNA 146a in neonatal rats following hypoxia injury. Neuroreport, 2015, 26(17), 1032-1038.
[http://dx.doi.org/10.1097/WNR.0000000000000463] [PMID: 26457369]
[88]
Mueller, M.; Zhou, J.; Yang, L.; Gao, Y.; Wu, F.; Schoeberlein, A.; Surbek, D.; Barnea, E.R.; Paidas, M.; Huang, Y. PreImplantation factor promotes neuroprotection by targeting microRNA let-7. Proc. Natl. Acad. Sci. USA, 2014, 111(38), 13882-13887.
[http://dx.doi.org/10.1073/pnas.1411674111] [PMID: 25205808]
[89]
Sun, P.; Liu, D.Z.; Jickling, G.C.; Sharp, F.R.; Yin, K.J. MicroRNA-based therapeutics in central nervous system injuries. J. Cereb. Blood Flow Metab., 2018, 38(7), 1125-1148.
[http://dx.doi.org/10.1177/0271678X18773871] [PMID: 29708005]