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Previous studies have indicated that stem\u2010cell transplantation could be an effective treatment. However, little is known about the direct impact of transplanted cells on injured brain tissue. We wanted to help fill this knowledge gap and investigated effects of hematopoietic stem\/progenitor cells (HSPCs) on the cerebral microcirculation after ischemia\u2010reperfusion injury (I\/RI). Treatment of HSPCs in I\/RI for up to 2 wk after cerebral I\/RI led to decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation, and reduced cerebral leukocyte adhesion. Confocal microscopy and fluorescence\u2010activated cell sorting analyses showed transplanted HSPCs emigrate preferentially into ischemic cortex brain parenchyma. We isolated migrated HSPCs from the brain; using RNA sequencing to investigate the transcriptome, we found metallothionein (MT, particularly MT\u2010I) transcripts were dramatically up\u2010regulated. Finally, to confirm the significance of MT, we exogenously administered MT\u2010I after cerebral I\/RI and found that it produced neuroprotection in a manner similar to HSPC treatment. These findings provide novel evidence that the mechanism through which HSPCs promote repair after stroke maybe\n                    <jats:italic>via<\/jats:italic>\n                    direct action of HSPC\u2010derived MT\u2010I and could therefore be exploited as a useful therapeutic strategy for stroke.\u2014Smith, H. K., Omura, S., Vital, S. A., Becker, F., Senchenkova, E. Y., Kaur, G., Tsunoda, I., Peirce, S. M., Gavins, F. N. E. Metallothionein I as a direct link between therapeutic hematopoietic stem\/progenitor cells and cerebral protection in stroke. FASEB J. 32, 2381\u20132394 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700746r","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T14:26:26Z","timestamp":1513866386000},"page":"2381-2394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Metallothionein I as a direct link between therapeutic hematopoietic stem\/progenitor cells and cerebral protection in stroke"],"prefix":"10.1096","volume":"32","author":[{"given":"Helen K.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichi","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantel A.","family":"Vital","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Y.","family":"Senchenkova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaganpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayn M.","family":"Peirce","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center\u2013Shreveport Shreveport Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicity N. 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