TAT-Hsp70 induces neuroprotection against stroke via anti-inflammatory actions providing appropriate cellular microenvironment for transplantation of neural precursor cells
2013 | Zeitschriftenartikel; Forschungsarbeit. Eine Publikation mit Affiliation zur Georg-August-Universität Göttingen.
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Zitiervorschlag
TAT-Hsp70 induces neuroprotection against stroke via anti-inflammatory actions providing appropriate cellular microenvironment for transplantation of neural precursor cells
Doeppner, T. R. ; Kaltwasser, B.; Jin Fengyan, J. F.; Hermann, D. M. & Bähr, M. (2013)
Journal of Cerebral Blood Flow & Metabolism, 33(11) pp. 1778-1788. DOI: https://doi.org/10.1038/jcbfm.2013.126
Dokumente & Medien
Details
- Autor(en)
- Doeppner, T. R. ; Kaltwasser, B.; Jin Fengyan, J. F.; Hermann, D. M.; Bähr, M.
- Zusammenfassung
- 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-brain 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-kappa B) as well as proteasomal degradation of the NF-kappa B regulator Ikappa B alpha (I kappa B-alpha) 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.
- Erscheinungsdatum
- 2013
- Zeitschrift
- Journal of Cerebral Blood Flow & Metabolism
- ISSN
- 0271-678X
- eISSN
- 1559-7016
- Sprache
- Englisch