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Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice

Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequenc...

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Autores principales: Doeppner, T R, Kaltwasser, B, Teli, M K, Bretschneider, E, Bähr, M, Hermann, D M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454329/
https://www.ncbi.nlm.nih.gov/pubmed/25144721
http://dx.doi.org/10.1038/cddis.2014.359
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author Doeppner, T R
Kaltwasser, B
Teli, M K
Bretschneider, E
Bähr, M
Hermann, D M
author_facet Doeppner, T R
Kaltwasser, B
Teli, M K
Bretschneider, E
Bähr, M
Hermann, D M
author_sort Doeppner, T R
collection PubMed
description Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood–brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment.
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spelling pubmed-44543292015-06-15 Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice Doeppner, T R Kaltwasser, B Teli, M K Bretschneider, E Bähr, M Hermann, D M Cell Death Dis Original Article Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood–brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. Nature Publishing Group 2014-08 2014-08-21 /pmc/articles/PMC4454329/ /pubmed/25144721 http://dx.doi.org/10.1038/cddis.2014.359 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Doeppner, T R
Kaltwasser, B
Teli, M K
Bretschneider, E
Bähr, M
Hermann, D M
Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title_full Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title_fullStr Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title_full_unstemmed Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title_short Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
title_sort effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454329/
https://www.ncbi.nlm.nih.gov/pubmed/25144721
http://dx.doi.org/10.1038/cddis.2014.359
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