{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:16:41Z","timestamp":1791400601461,"version":"4.3.3"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulating repair processes. We investigated whether MSC treatment improves recovery after neonatal stroke and whether MSC overexpressing brain-derived neurotrophic factor (MSC-BDNF) further enhances recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>We performed 1.5-hour transient middle cerebral artery occlusion in 10-day-old rats. Three days after reperfusion, pups with evidence of injury by diffusion-weighted MRI were treated intranasally with MSC, MSC-BDNF, or vehicle. To determine the effect of MSC treatment, brain damage, sensorimotor function, and cerebral cell proliferation were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>Intranasal delivery of MSC- and MSC-BDNF significantly reduced infarct size and gray matter loss in comparison with vehicle-treated rats without any significant difference between MSC- and MSC-BDNF\u2013treatment. Treatment with MSC-BDNF significantly reduced white matter loss with no significant difference between MSC- and MSC-BDNF\u2013treatment. Motor deficits were also improved by MSC treatment when compared with vehicle-treated rats. MSC-BDNF\u2013treatment resulted in an additional significant improvement of motor deficits 14 days after middle cerebral artery occlusion, but there was no significant difference between MSC or MSC-BDNF 28 days after middle cerebral artery occlusion. Furthermore, treatment with either MSC or MSC-BDNF induced long-lasting cell proliferation in the ischemic hemisphere.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Intranasal administration of MSC after neonatal stroke is a promising therapy for treatment of neonatal stroke. In this experimental paradigm, MSC- and BNDF-hypersecreting MSC are equally effective in reducing ischemic brain damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.111.000326","type":"journal-article","created":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T01:41:27Z","timestamp":1364521287000},"page":"1426-1432","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":184,"title":["Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke"],"prefix":"10.1161","volume":"44","author":[{"given":"Cindy T.J.","family":"van Velthoven","sequence":"first","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Ann","family":"Sheldon","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Kavelaars","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Derugin","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinaida S.","family":"Vexler","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke L.D.M.","family":"Willemen","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Maas","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cobi J.","family":"Heijnen","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Ferriero","sequence":"additional","affiliation":[{"name":"From the Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, the Netherlands (C.T.J.v.V., H.L.D.M.W., M.M., C.J.H.); Departments of Neurology and Pediatrics, University of California San Francisco, San Francisco, CA (R.A.S., N.D., Z.S.V., D.M.F.); and Department of Symptom Research, University of Texas, MD Anderson Cancer Centre, Houston, TX (A.K., C.J.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041996"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2008.09.018"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00557-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.10.017"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.021"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2007.00792.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1835-10.2010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.05.055"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(98)00096-0"},{"key":"e_1_3_3_11_2","first-page":"419","article-title":"Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage.","volume":"68","author":"van Velthoven CT","year":"2010","unstructured":"van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. 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