{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:29:48Z","timestamp":1777793388295,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T00:00:00Z","timestamp":1374624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Heat-shock protein 70 (Hsp70) protects against cerebral ischemia, which is attributed to its chaperone activity. However, recent reports also describe pro-inflammatory actions of Hsp70 via activation of Toll-like receptors (TLR). Using membrane-permeable transactivator of transcription (TAT)-Hsp70, we analyzed TAT-Hsp70-induced neuroprotection and its underlying mechanism after cerebral ischemia in mice. Infusion of TAT-Hsp70 reduced infarct volume and enhanced blood\u2013brain barrier integrity on day 3 poststroke, when given no later than 12 hours. The latter was associated with reduction of microglial activation, although upregulation of pro-inflammatory TLR-2\/4 was observed both in verum and in control animals. Nevertheless, protein abundance and nuclear translocation of downstream nuclear factor kappa B (NF-\u03baB) as well as proteasomal degradation of the NF-\u03baB regulator Ikappa B alpha (I\u03baB-\u03b1) were significantly reduced by TAT-Hsp70. TAT-Hsp70-induced neuroprotection and functional recovery were restricted to 4 weeks only. However, TAT-Hsp70 provided an appropriate extracellular milieu for delayed intravenous transplantation of adult neural precursor cells (NPCs). Thus, NPCs that were grafted 28 days poststroke induced long-term neuroprotection for at least 3 months, which was not due to integration of grafted cells but rather due to paracrine effects of transplanted NPCs. Conclusively, TAT-Hsp70 ameliorates postischemic inflammation via proteasome inhibition, thus providing an appropriate extracellular milieu for delayed NPC transplantation and culminating in long-term neuroprotection.<\/jats:p>","DOI":"10.1038\/jcbfm.2013.126","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T04:29:29Z","timestamp":1374640169000},"page":"1778-1788","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["TAT-Hsp70 Induces Neuroprotection Against Stroke Via Anti-Inflammatory Actions Providing Appropriate Cellular Microenvironment for Transplantation of Neural Precursor Cells"],"prefix":"10.1177","volume":"33","author":[{"given":"Thorsten R","family":"Doeppner","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Duisburg-Essen Medical School, Essen, Germany"},{"name":"Department of Neurology, University of Goettingen Medical 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