{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:37:21Z","timestamp":1790638641206,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1D1A1B03033979"],"award-info":[{"award-number":["NRF-2017R1D1A1B03033979"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI18C0560"],"award-info":[{"award-number":["HI18C0560"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Closely linked to Alzheimer\u2019s disease (AD), the pathological spectrum of vascular cognitive impairment (VCI) is known to be wide and complex. Considering that multiple instead of a single targeting approach is considered a treatment option for such complicated diseases, the multifaceted aspects of mesenchymal stem cells (MSCs) make them a suitable candidate to tackle the heterogeneity of VCI. MSCs were delivered via the intracerebroventricular (ICV) route in mice that were subjected to VCI by carotid artery stenosis. VCI was induced in C57BL6\/J mice wild type (C57VCI) mice by applying a combination of ameroid constrictors and microcoils, while ameroid constrictors alone were bilaterally applied to 5xFAD (transgenic AD mouse model) mice (5xVCI). Compared to the controls (minimal essential medium (MEM)-injected C57VCI mice), changes in spatial working memory were not noted in the MSC-injected C57VCI mice, and unexpectedly, the mortality rate was higher. In contrast, compared to the MEM-injected 5xVCI mice, mortality was not observed, and the spatial working memory was also improved in MSC-injected 5xVCI mice. Disease progression of the VCI-induced mice seems to be affected by the method of carotid artery stenosis and due to this heterogeneity, various factors must be considered to maximize the therapeutic benefits exerted by MSCs. Factors, such as the optimal MSC injection time point, cell concentration, sacrifice time point, and immunogenicity of the transplanted cells, must all be adequately addressed so that MSCs can be appropriately and effectively used as a treatment option for VCI.<\/jats:p>","DOI":"10.3390\/ijms21155524","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"5524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-2562","authenticated-orcid":false,"given":"Na Kyung","family":"Lee","sequence":"first","affiliation":[{"name":"School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-6472","authenticated-orcid":false,"given":"Hyeongseop","family":"Kim","sequence":"additional","affiliation":[{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Wook","family":"Chang","sequence":"additional","affiliation":[{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyemin","family":"Jang","sequence":"additional","affiliation":[{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunnyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Samsung Biomedical Research Institute, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehoon","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Samsung Biomedical Research Institute, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Samsung Biomedical Research Institute, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8655-3495","authenticated-orcid":false,"given":"Jeong Pyo","family":"Son","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Osong Medical Innovation Foundation, Cheongju 28160, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[{"name":"School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1111\/j.1471-4159.2010.06958.x","article-title":"Experimental models of vascular dementia and vascular cognitive impairment: A systematic review","volume":"115","author":"Jiwa","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Attems, J., and Jellinger, K.A. (2014). The overlap between vascular disease and Alzheimer\u2019s disease\u2014Lessons from pathology. BMC Med., 12.","DOI":"10.1186\/s12916-014-0206-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1212\/WNL.0b013e318221acee","article-title":"Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B","volume":"77","author":"Lee","year":"2011","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.neuron.2013.10.008","article-title":"The pathobiology of vascular dementia","volume":"80","author":"Iadecola","year":"2013","journal-title":"Neuron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S293","DOI":"10.3233\/JAD-180899","article-title":"Vascular Mild Cognitive Impairment: Identifying Disease in Community-Dwelling Older Adults, Reducing Risk Factors, and Providing Support. The Osaki-Tajiri and Kurihara Projects","volume":"70","author":"Meguro","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1016\/j.jacc.2019.04.034","article-title":"Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel","volume":"73","author":"Iadecola","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s10571-015-0286-3","article-title":"Animal Models of Vascular Cognitive Impairment and Dementia (VCID)","volume":"36","author":"Gooch","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1161\/STROKEAHA.116.012066","article-title":"Vascular Contributions to Cognitive Impairment and Dementia: Topical Review of Animal Models","volume":"47","author":"Madigan","year":"2016","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s12975-016-0486-2","article-title":"Rodent Models of Vascular Cognitive Impairment","volume":"7","author":"Yang","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hort, J., Valis, M., Kuca, K., and Angelucci, F. (2019). Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102405"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0306-3623(97)00284-X","article-title":"Rodent models of global cerebral ischemia: A comparison of two-vessel occlusion and four-vessel occlusion","volume":"30","author":"McBean","year":"1998","journal-title":"Gen. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.21769\/BioProtoc.262","article-title":"Mouse Transient Global Ischemia Two-Vessel Occlusion Model","volume":"2","author":"Pontarelli","year":"2012","journal-title":"Bio Protoc."},{"key":"ref_13","first-page":"e59078","article-title":"Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion","volume":"145","author":"Chen","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1523\/JNEUROSCI.3970-14.2015","article-title":"A novel mouse model of subcortical infarcts with dementia","volume":"35","author":"Hattori","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lee, N.K., Kim, H., Yang, J., Kim, J., Son, J.P., Jang, H., and Na, D.L. (2020). Heterogeneous Disease Progression in a Mouse Model of Vascular Cognitive Impairment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082820"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1172\/JCI97509","article-title":"Blood will out: Vascular contributions to Alzheimer\u2019s disease","volume":"128","author":"Strickland","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fnins.2016.00177","article-title":"One for All? Hitting Multiple Alzheimer\u2019s Disease Targets with One Drug","volume":"10","author":"Hughes","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.tips.2020.04.008","article-title":"A Perspective on Multi-target Drugs for Alzheimer\u2019s Disease","volume":"41","author":"Benek","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9896","DOI":"10.1523\/JNEUROSCI.1762-16.2016","article-title":"Reduced Efficacy of Anti-Abeta Immunotherapy in a Mouse Model of Amyloid Deposition and Vascular Cognitive Impairment Comorbidity","volume":"36","author":"Weekman","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.2174\/1570159X15666171016164734","article-title":"Potential Therapeutics for Vascular Cognitive Impairment and Dementia","volume":"16","author":"Sun","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/cdd.2011.140","article-title":"Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-beta plaques","volume":"19","author":"Kim","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s12272-016-0799-4","article-title":"Activin A secreted by human mesenchymal stem cells induces neuronal development and neurite outgrowth in an in vitro model of Alzheimer\u2019s disease: Neurogenesis induced by MSCs via activin A","volume":"39","author":"Park","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"39340","DOI":"10.1038\/srep39340","article-title":"Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer\u2019s Disease Model","volume":"7","author":"Lee","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","first-page":"629","article-title":"Killing two birds with one stone: The multifunctional roles of mesenchymal stem cells in the treatment of neurodegenerative and muscle diseases","volume":"33","author":"Lee","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00109-019-01752-6","article-title":"Exploring the roles of MSCs in infections: Focus on bacterial diseases","volume":"97","author":"Marrazzo","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_26","first-page":"95","article-title":"Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer\u2019s disease dementia: A phase 1 clinical trial","volume":"1","author":"Kim","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_27","first-page":"533","article-title":"Optimal mesenchymal stem cell delivery routes to enhance neurogenesis for the treatment of Alzheimer\u2019s disease: Optimal MSCs delivery routes for the treatment of AD","volume":"33","author":"Park","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jiang, W., Gong, L., Liu, F., and Mu, J. (2020). Stem cells and vascular dementia: From basic science to the clinic. Cell Tissue Bank.","DOI":"10.1007\/s10561-020-09829-0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1212\/01.WNL.0000118211.78503.F5","article-title":"Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology","volume":"62","author":"Schneider","year":"2004","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0140-6736(99)02355-7","article-title":"Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer\u2019s disease","volume":"354","author":"Esiri","year":"1999","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/ana.21142","article-title":"Subcortical infarcts, Alzheimer\u2019s disease pathology, and memory function in older persons","volume":"62","author":"Schneider","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ana.25246","article-title":"Combined neuropathological pathways account for age-related risk of dementia","volume":"84","author":"Power","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.neurobiolaging.2008.09.011","article-title":"Contribution of vascular pathology to the clinical expression of dementia","volume":"31","author":"Strozyk","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3988\/jcn.2006.2.1.1","article-title":"Small vessel disease and subcortical vascular dementia","volume":"2","author":"Kalaria","year":"2006","journal-title":"J. Clin. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e002757","DOI":"10.1161\/JAHA.115.002757","article-title":"Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans","volume":"5","author":"Hattori","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/ni.1781","article-title":"Foamy macrophages and the progression of the human tuberculosis granuloma","volume":"10","author":"Russell","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1293\/tox.26.55","article-title":"Availability of a microglia and macrophage marker, iba-1, for differential diagnosis of spontaneous malignant reticuloses from astrocytomas in rats","volume":"26","author":"Nakamura","year":"2013","journal-title":"J. Toxicol. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1042\/CS20160727","article-title":"Chronic cerebral hypoperfusion: A key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia","volume":"131","author":"Duncombe","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0166-4328(02)00090-6","article-title":"Persistent impairment of gait performances and working memory after bilateral common carotid artery occlusion in the adult Wistar rat","volume":"136","author":"Sarti","year":"2002","journal-title":"Behav. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.3727\/096368916X690818","article-title":"Mesenchymal Stem Cells as Treatment for Behavioral Deficits and Neuropathology in the 5xFAD Mouse Model of Alzheimer\u2019s Disease","volume":"25","author":"Pappas","year":"2016","journal-title":"Cell Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.bbrc.2017.08.115","article-title":"Lowering the concentration affects the migration and viability of intracerebroventricular-delivered human mesenchymal stem cells","volume":"493","author":"Kim","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40425-018-0371-5","article-title":"Dexamethasone-induced immunosuppression: Mechanisms and implications for immunotherapy","volume":"6","author":"Giles","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1517\/17425247.2016.1171315","article-title":"CSF, blood-brain barrier, and brain drug delivery","volume":"13","author":"Pardridge","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hwang, J.W., Lee, N.K., Yang, J.H., Son, H.J., Bang, S.I., Chang, J.W., and Na, D.L. (2020). A Comparison of Immune Responses Exerted Following Syngeneic, Allogeneic, and Xenogeneic Transplantation of Mesenchymal Stem Cells into the Mouse Brain. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093052"},{"key":"ref_45","first-page":"1","article-title":"Allogeneic ADSCs induce CD8 T cell-mediated cytotoxicity and faster cell death after exposure to xenogeneic serum or proinflammatory cytokines","volume":"51","author":"Chang","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Washida, K., Hattori, Y., and Ihara, M. (2019). Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246176"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2324.e7","DOI":"10.1016\/j.neurobiolaging.2010.09.005","article-title":"Selective white matter pathology induces a specific impairment in spatial working memory","volume":"32","author":"Coltman","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/ana.20503","article-title":"Correlates of hippocampal neuron number in Alzheimer\u2019s disease and ischemic vascular dementia","volume":"57","author":"Zarow","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fnagi.2014.00010","article-title":"Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation, hyperphosphorylation of tau and behavioral deficits in mice","volume":"6","author":"Zhao","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ahn, S.Y., Chang, Y.S., Sung, D.K., Sung, S.I., Yoo, H.S., Im, G.H., Choi, S.J., and Park, W.S. (2015). Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132919"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.pbb.2005.05.004","article-title":"Choto-san, a Kampo formula, improves chronic cerebral hypoperfusion-induced spatial learning deficit via stimulation of muscarinic M1 receptor","volume":"81","author":"Murakami","year":"2005","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.brainresbull.2011.10.006","article-title":"Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment","volume":"87","author":"Cechetti","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1523\/JNEUROSCI.21-17-06706.2001","article-title":"Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus","volume":"21","author":"Pencea","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.neuroscience.2015.10.055","article-title":"BMSCs transplantation improves cognitive impairment via up-regulation of hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion","volume":"311","author":"Long","year":"2015","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9058","DOI":"10.1038\/srep09058","article-title":"Magnetic resonance imaging with superparamagnetic iron oxide fails to track the long-term fate of mesenchymal stem cells transplanted into heart","volume":"5","author":"Ma","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1080\/14653240410005041","article-title":"Mesenchymal stem\/progenitor cells developed in cultures from UC blood","volume":"6","author":"Yang","year":"2004","journal-title":"Cytotherapy"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lee, N.K., Kim, H.S., Yoo, D., Hwang, J.W., Choi, S.J., Oh, W., Chang, J.W., and Na, D.L. (2016). Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain. Stem Cell Rev.","DOI":"10.1007\/s12015-016-9694-0"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13023-015-0337-3","article-title":"Decreased performance in IDUA knockout mouse mimic limitations of joint function and locomotion in patients with Hurler syndrome","volume":"10","author":"Kim","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lee, N.K., Yang, J., Chang, E.H., Park, S.E., Lee, J., Choi, S.J., Oh, W., Chang, J.W., and Na, D.L. (2016). Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer\u2019s Disease Mouse Model. 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