{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:10:38Z","timestamp":1792501838923,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T00:00:00Z","timestamp":1541462400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"DOI":"10.3389\/fneur.2018.00931","type":"journal-article","created":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T11:28:05Z","timestamp":1541503685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":63,"title":["MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage"],"prefix":"10.3389","volume":"9","author":[{"given":"Heyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuting","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,11,6]]},"reference":[{"key":"B1","first-page":"1632","article-title":"Intracerebral haemorrhage","volume-title":"Lancet","author":"Qureshi","year":"2009"},{"key":"B2","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/s1474-4422(12)70104-7","article-title":"Intracerebral haemorrhage: mechanisms of injury and therapeutic targets","volume":"11","author":"Keep","year":"2012","journal-title":"Lancet Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1002\/ana.24159","article-title":"Toll-like receptor 2\/4 heterodimer mediates inflammatory injury in intracerebral hemorrhage","volume":"75","author":"Wang","year":"2014","journal-title":"Ann Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1007\/s00011-015-0845-6","article-title":"Gene delivery with IFN-gamma-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis","volume":"64","author":"Chen","year":"2015","journal-title":"Inflamm Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1093\/eurheartj\/ehv136","article-title":"Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial)","volume":"36","author":"Mathiasen","year":"2015","journal-title":"Eur Heart J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e00191","DOI":"10.1042\/bsr20150025","article-title":"Human mesenchymal stem cells - current trends and future prospective","volume":"35","author":"Ullah","year":"2015","journal-title":"Biosci Rep"},{"key":"B7","first-page":"2271","article-title":"The stem cell secretome and its role in brain repair","volume-title":"Biochimie","author":"Drago","year":"2013"},{"key":"B8","first-page":"11","article-title":"The MSC: an injury drugstore","volume-title":"Cell Stem Cell","author":"Caplan","year":"2011"},{"key":"B9","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/s1474-4422(11)70121-1","article-title":"Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases","volume":"10","author":"Uccelli","year":"2011","journal-title":"Lancet Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/jnr.10691","article-title":"Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat","volume":"73","author":"Chen","year":"2003","journal-title":"J Neurosci Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"14638","DOI":"10.1073\/pnas.0803670105","article-title":"Stem\/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory\/immune responses","volume":"105","author":"Ohtaki","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1073\/pnas.042678299","article-title":"Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery","volume":"99","author":"Hofstetter","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B13","first-page":"120","article-title":"Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells","volume-title":"Gene","author":"Liu","year":"2012"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1080\/01616412.2016.1232013","article-title":"Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats","volume":"38","author":"Altintas","year":"2016","journal-title":"Neurol Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1177\/0300060516630852","article-title":"Differential expression of circulating microRNAs in blood and haematoma samples from patients with intracerebral haemorrhage","volume":"44","author":"Wang","year":"","journal-title":"J Int Med Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1582-4934.2008.00556.x","article-title":"miR-21: a small multi-faceted RNA","volume":"13","author":"Krichevsky","year":"2009","journal-title":"J Cell Mol Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s12032-014-0057-x","article-title":"High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation","volume":"31","author":"Dong","year":"2014","journal-title":"Med Oncol"},{"key":"B18","first-page":"28867","article-title":"MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN\/Akt pathway","volume-title":"Oncotarget","author":"He","year":"2015"},{"key":"B19","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.yexcr.2015.08.010","article-title":"MiR-21 inhibits autophagy by targeting Rab11a in renal ischemia\/reperfusion","volume":"338","author":"Liu","year":"2015","journal-title":"Exp Cell Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"17935","DOI":"10.1523\/jneurosci.3860-12.2012","article-title":"microRNA-21 regulates astrocytic response following spinal cord injury","volume":"32","author":"Bhalala","year":"2012","journal-title":"J Neurosci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1007\/s11033-014-3820-3","article-title":"MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG","volume":"42","author":"Shang","year":"2015","journal-title":"Mol Biol Rep"},{"key":"B22","first-page":"98","article-title":"miR-21 and miR-145 cooperation in regulation of colon cancer stem cells","volume-title":"Mol Cancer","author":"Yu","year":"2015"},{"key":"B23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.3109\/07357907.2015.1019676","article-title":"Abnormal Expression of miR-21 and miR-95 in cancer stem-like cells is associated with radioresistance of lung cancer","volume":"33","author":"Zhang","year":"2015","journal-title":"Cancer Invest"},{"key":"B24","first-page":"144","article-title":"MiR-21 functions oppositely in proliferation and differentiation of neural stem\/precursor cells via regulating AKT and GSK-3beta","volume-title":"Cell Mol Biol (Noisy-le-grand)","author":"Gao","year":"2016"},{"key":"B25","first-page":"29161","article-title":"Bone marrow-derived mesenchymal stem cells overexpressing MiR-21 efficiently repair myocardial damage in rats","volume-title":"Oncotarget","author":"Zeng","year":"2017"},{"key":"B26","first-page":"801","article-title":"Collagenase-induced intracerebral hemorrhage in rats","volume-title":"Stroke","author":"Rosenberg","year":"1990"},{"key":"B27","first-page":"2478","article-title":"Behavioral tests after intracerebral hemorrhage in the rat","volume-title":"Stroke","author":"Hua","year":"2002"},{"key":"B28","first-page":"616","article-title":"Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke","volume-title":"Brain","author":"Lee","year":"2008"},{"key":"B29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/978-1-4939-6728-5_3","article-title":"Immuno-characterization of exosomes using nanoparticle tracking analysis","volume":"1545","author":"McNicholas","year":"2017","journal-title":"Methods Mol Biol"},{"key":"B30","first-page":"970","article-title":"MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease","volume-title":"Leukemia","author":"Kordelas","year":"2014"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1007\/s10072-014-1657-0","article-title":"NF-kappaB activation and cell death after intracerebral hemorrhage in patients","volume":"35","author":"Zhang","year":"2014","journal-title":"Neurol Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s11011-012-9301-2","article-title":"Activation of acetylcholinesterase after U-74389G administration in a porcine model of intracerebral hemorrhage","volume":"27","author":"Bimpis","year":"2012","journal-title":"Metab Brain Dis"},{"key":"B33","first-page":"S35","article-title":"Advances in the management of intracerebral hemorrhage","volume-title":"J Neural Transm (Vienna)","author":"Kuramatsu","year":"2013"},{"key":"B34","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3727\/096368916x694193","article-title":"Mesenchymal stem cells: the magic cure for intraventricular hemorrhage?","volume":"26","author":"Park","year":"2017","journal-title":"Cell Transplant"},{"key":"B35","first-page":"1739","article-title":"Alteration in abundance and compartmentalization of inflammation-related miRNAs in plasma after intracerebral hemorrhage","volume-title":"Stroke","author":"Guo","year":"2013"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1007\/s12035-015-9099-0","article-title":"High Serum MiR-130a levels are associated with severe perihematomal edema and predict adverse outcome in acute ICH","volume":"53","author":"Wang","year":"2016","journal-title":"Mol Neurobiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.brainres.2014.07.045","article-title":"miR-21 alleviated apoptosis of cortical neurons through promoting PTEN-Akt signaling pathway in vitro after experimental traumatic brain injury","volume":"1582","author":"Han","year":"2014","journal-title":"Brain Res"},{"key":"B38","first-page":"1033","article-title":"Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis","volume-title":"Stroke","author":"Zille","year":"2017"},{"key":"B39","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s13287-017-0722-z","article-title":"MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction","volume":"8","author":"Chen","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"B40","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.bbrc.2016.01.084","article-title":"MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal","volume":"470","author":"Shi","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"B41","first-page":"901","article-title":"Transplanted bone marrow regenerates liver by cell fusion","volume-title":"Nature","author":"Vassilopoulos","year":"2003"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0019569","article-title":"Human bone marrow-derived stem cells acquire epithelial characteristics through fusion with gastrointestinal epithelial cells","volume-title":"PLoS ONE","author":"Ferrand","year":"2011"},{"key":"B43","first-page":"1390","article-title":"Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease","volume-title":"Transplantation","author":"Ringden","year":"2006"},{"key":"B44","first-page":"54","article-title":"Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6","volume-title":"Cell Stem Cell","author":"Lee","year":"2009"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.febslet.2015.03.031","article-title":"Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration","volume":"589","author":"Nakamura","year":"2015","journal-title":"FEBS Lett"},{"key":"B46","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13045-015-0220-7","article-title":"Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma","volume":"8","author":"Lou","year":"2015","journal-title":"J Hematol Oncol"},{"key":"B47","first-page":"590","article-title":"LTRPC7 is a Mg .ATP-regulated divalent cation channel required for cell viability","volume-title":"Nature","author":"Nadler","year":"2001"},{"key":"B48","first-page":"1043","article-title":"TRP-PLIK, a bifunctional protein with kinase and ion channel activities","volume-title":"Science","author":"Runnels","year":"2001"},{"key":"B49","first-page":"863","article-title":"A key role for TRPM7 channels in anoxic neuronal death","volume-title":"Cell","author":"Aarts","year":"2003"},{"key":"B50","first-page":"2425","article-title":"Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death","volume-title":"Antioxid Redox Signal","author":"Nunez-Villena","year":"2011"},{"key":"B51","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/aps.2011.47","article-title":"Calcium-permeable ion channels involved in glutamate receptor-independent ischemic brain injury","volume":"32","author":"Li","year":"2011","journal-title":"Acta Pharmacol Sin"},{"key":"B52","first-page":"367","article-title":"IL-1beta induces GFAP expression in vitro and in vivo and protects neurons from traumatic injury-associated apoptosis in rat brain striatum via NFkappaB\/Ca(2)(+)-calmodulin\/ERK mitogen-activated protein kinase signaling pathway","volume-title":"Neuroscience","author":"Sticozzi","year":"2013"},{"key":"B53","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.imlet.2014.03.005","article-title":"Curcumin inhibits microglia inflammation and confers neuroprotection in intracerebral hemorrhage","volume":"160","author":"Yang","year":"2014","journal-title":"Immunol Lett"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fneur.2018.00931\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T11:28:11Z","timestamp":1541503691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fneur.2018.00931\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,6]]},"references-count":53,"alternative-id":["10.3389\/fneur.2018.00931"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2018.00931","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,6]]},"article-number":"931"}}