{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:28:58Z","timestamp":1790033338474,"version":"4.0.1"},"reference-count":39,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>\n                    Intra-arterial neural stem cell (NSC) therapy has the potential to improve long-term outcomes after stroke. Here we evaluate if pretreatment of NSCs with brain-derived neurotrophic factor (BDNF) prior to transplantation improves cell engraftment and functional recovery following hypoxic\u2013ischemic (HI) stroke. Human embryonic-derived NSCs with or without BDNF pretreatment (1 h, 100 ng\/ml) were transplanted 3 days after HI stroke. Functional recovery was assessed using the horizontal ladder test. Cell engraftment was evaluated using bioluminescence imaging (BLI) and histological counts of SC121\n                    <jats:sup>+<\/jats:sup>\n                    cells. Fluoro-Jade C (FJC) and NeuN stains were used to evaluate neuroprotection. The effect of BDNF on NSCs was analyzed using a migration assay, immunocytochemistry, Luminex proteomic assay, and RT-qPCR.BLI analysis demonstrated significantly higher photon flux in the BDNF-treated NSC group compared to untreated NSC ( p = 0.049) and control groups ( p = 0.0021) at 1 week after transplantation. Immunohistochemistry confirmed increased transplanted cell survival in the cortex ( p = 0.0126) and hippocampus ( p = 0.0098) of animals injected with BDNF-treated NSCs compared to untreated NSCs. Behavioral testing revealed that the BDNF-treated NSC group demonstrated increased sensorimotor recovery compared to the untreated NSC and control groups ( p &lt; 0.001) over the 1-month period ( p &lt; 0.001) following transplantation. A significant improvement in performance was found in the BDNF-treated NSC group compared to the control group at 14, 21, and 28 ( p &lt; 0.05) days after transplantation. The cortex and hippocampus of the BDNF-treated NSC group had significantly more SC121\n                    <jats:sup>+<\/jats:sup>\n                    NSCs ( p = 0.0125, p = 0.0098), fewer FJC\n                    <jats:sup>+<\/jats:sup>\n                    neurons ( p = 0.0370, p = 0.0285), and a higher percentage of NeuN\n                    <jats:sup>+<\/jats:sup>\n                    expression ( p= 0.0354) in the cortex compared to the untreated NSC group. BDNF treatment of NSCs resulted in significantly greater migration to SDF-1, secretion of M-CSF, VEGF, and expression of CXCR4, VCAM-1, Thrombospondins 1 and 2, and BDNF. BDNF pretreatment of NSCs results in higher initial NSC engraftment and survival, increased neuroprotection, and greater functional recovery when compared to untreated NSCs.\n                  <\/jats:p>","DOI":"10.3727\/096368914x679354","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T23:04:44Z","timestamp":1393887884000},"page":"2449-2461","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":67,"title":["BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery after Transplantation in Hypoxic\u2013Ischemic Stroke"],"prefix":"10.1177","volume":"24","author":[{"given":"Sahar","family":"Rosenblum","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Department of Neurosurgery, University of Basel, Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenille N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Department of Neurosurgery, University of Basel, Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua Y.","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Westbroek","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendrick","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Department of Neurosurgery, University of Basel, Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"bibr1-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1038\/374450a0"},{"key":"bibr2-096368914X679354","doi-asserted-by":"publisher","DOI":"10.2174\/156720206776875849"},{"key":"bibr3-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.606368"},{"key":"bibr4-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr094"},{"key":"bibr5-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-011-0093-1"},{"key":"bibr6-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20501"},{"key":"bibr7-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-05149.2003"},{"key":"bibr8-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)03371-6"},{"key":"bibr9-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.517474"},{"key":"bibr10-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.020"},{"key":"bibr11-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.213"},{"key":"bibr12-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903030"},{"key":"bibr13-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.500470"},{"key":"bibr14-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.12.026"},{"key":"bibr15-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.1.84"},{"key":"bibr16-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1002\/stem.584"},{"key":"bibr17-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.677"},{"key":"bibr18-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.surneu.2005.12.028"},{"key":"bibr19-096368914X679354","doi-asserted-by":"publisher","DOI":"10.2174\/156720209787466028"},{"key":"bibr20-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000156"},{"key":"bibr21-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005586"},{"key":"bibr22-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22474"},{"key":"bibr23-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1666"},{"key":"bibr24-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2008.65"},{"key":"bibr25-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0584-1"},{"key":"bibr26-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1038\/nn1827"},{"key":"bibr27-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh162"},{"key":"bibr28-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(02)00012-2"},{"key":"bibr29-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.06.035"},{"key":"bibr30-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.575993"},{"key":"bibr31-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.06.021"},{"key":"bibr32-096368914X679354","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.06.084"},{"issue":"2","key":"bibr33-096368914X679354","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1242\/jcs.115.2.283","volume":"115","author":"Prag 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