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Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI results in a prolonged secondary central neuro-inflammatory response. Previously, we have demonstrated that multiple doses (2 and 24 h after TBI) of multipotent adult progenitor cells (MAPC) delivered intravenousl...

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Autores principales: Bedi, Supinder S., Aertker, Benjamin M., Liao, George P., Caplan, Henry W., Bhattarai, Deepa, Mandy, Fanni, Mandy, Franciska, Fernandez, Luis G., Zelnick, Pamela, Mitchell, Matthew B., Schiffer, Walter, Johnson, Margaret, Denson, Emma, Prabhakara, Karthik, Xue, Hasen, Smith, Philippa, Uray, Karen, Olson, Scott D., Mays, Robert W., Cox, Charles S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856201/
https://www.ncbi.nlm.nih.gov/pubmed/29548333
http://dx.doi.org/10.1186/s12974-018-1122-8
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author Bedi, Supinder S.
Aertker, Benjamin M.
Liao, George P.
Caplan, Henry W.
Bhattarai, Deepa
Mandy, Fanni
Mandy, Franciska
Fernandez, Luis G.
Zelnick, Pamela
Mitchell, Matthew B.
Schiffer, Walter
Johnson, Margaret
Denson, Emma
Prabhakara, Karthik
Xue, Hasen
Smith, Philippa
Uray, Karen
Olson, Scott D.
Mays, Robert W.
Cox, Charles S.
author_facet Bedi, Supinder S.
Aertker, Benjamin M.
Liao, George P.
Caplan, Henry W.
Bhattarai, Deepa
Mandy, Fanni
Mandy, Franciska
Fernandez, Luis G.
Zelnick, Pamela
Mitchell, Matthew B.
Schiffer, Walter
Johnson, Margaret
Denson, Emma
Prabhakara, Karthik
Xue, Hasen
Smith, Philippa
Uray, Karen
Olson, Scott D.
Mays, Robert W.
Cox, Charles S.
author_sort Bedi, Supinder S.
collection PubMed
description BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI results in a prolonged secondary central neuro-inflammatory response. Previously, we have demonstrated that multiple doses (2 and 24 h after TBI) of multipotent adult progenitor cells (MAPC) delivered intravenously preserve the blood-brain barrier (BBB), improve spatial learning, and decrease activated microglia/macrophages in the dentate gyrus of the hippocampus. In order to determine if there is an optimum treatment window to preserve the BBB, improve cognitive behavior, and attenuate the activated microglia/macrophages, we administered MAPC at various clinically relevant intervals. METHODS: We administered two injections intravenously of MAPC treatment at hours 2 and 24 (2/24), 6 and 24 (6/24), 12 and 36 (12/36), or 36 and 72 (36/72) post cortical contusion injury (CCI) at a concentration of 10 million/kg. For BBB experiments, animals that received MAPC at 2/24, 6/24, and 12/36 were euthanized 72 h post injury. The 36/72 treated group was harvested at 96 h post injury. RESULTS: Administration of MAPC resulted in a significant decrease in BBB permeability when administered at 2/24 h after TBI only. For behavior experiments, animals were harvested post behavior paradigm. There was a significant improvement in spatial learning (120 days post injury) when compared to cortical contusion injury (CCI) in groups when MAPC was administered at or before 24 h. In addition, there was a significant decrease in activated microglia/macrophages in the dentate gyrus of hippocampus of the treated group (2/24) only when compared to CCI. CONCLUSIONS: Intravenous injections of MAPC at or before 24 h after CCI resulted in improvement of the BBB, improved cognitive behavior, and attenuated activated microglia/macrophages in the dentate gyrus.
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spelling pubmed-58562012018-03-22 Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury Bedi, Supinder S. Aertker, Benjamin M. Liao, George P. Caplan, Henry W. Bhattarai, Deepa Mandy, Fanni Mandy, Franciska Fernandez, Luis G. Zelnick, Pamela Mitchell, Matthew B. Schiffer, Walter Johnson, Margaret Denson, Emma Prabhakara, Karthik Xue, Hasen Smith, Philippa Uray, Karen Olson, Scott D. Mays, Robert W. Cox, Charles S. J Neuroinflammation Research BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI results in a prolonged secondary central neuro-inflammatory response. Previously, we have demonstrated that multiple doses (2 and 24 h after TBI) of multipotent adult progenitor cells (MAPC) delivered intravenously preserve the blood-brain barrier (BBB), improve spatial learning, and decrease activated microglia/macrophages in the dentate gyrus of the hippocampus. In order to determine if there is an optimum treatment window to preserve the BBB, improve cognitive behavior, and attenuate the activated microglia/macrophages, we administered MAPC at various clinically relevant intervals. METHODS: We administered two injections intravenously of MAPC treatment at hours 2 and 24 (2/24), 6 and 24 (6/24), 12 and 36 (12/36), or 36 and 72 (36/72) post cortical contusion injury (CCI) at a concentration of 10 million/kg. For BBB experiments, animals that received MAPC at 2/24, 6/24, and 12/36 were euthanized 72 h post injury. The 36/72 treated group was harvested at 96 h post injury. RESULTS: Administration of MAPC resulted in a significant decrease in BBB permeability when administered at 2/24 h after TBI only. For behavior experiments, animals were harvested post behavior paradigm. There was a significant improvement in spatial learning (120 days post injury) when compared to cortical contusion injury (CCI) in groups when MAPC was administered at or before 24 h. In addition, there was a significant decrease in activated microglia/macrophages in the dentate gyrus of hippocampus of the treated group (2/24) only when compared to CCI. CONCLUSIONS: Intravenous injections of MAPC at or before 24 h after CCI resulted in improvement of the BBB, improved cognitive behavior, and attenuated activated microglia/macrophages in the dentate gyrus. BioMed Central 2018-03-16 /pmc/articles/PMC5856201/ /pubmed/29548333 http://dx.doi.org/10.1186/s12974-018-1122-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bedi, Supinder S.
Aertker, Benjamin M.
Liao, George P.
Caplan, Henry W.
Bhattarai, Deepa
Mandy, Fanni
Mandy, Franciska
Fernandez, Luis G.
Zelnick, Pamela
Mitchell, Matthew B.
Schiffer, Walter
Johnson, Margaret
Denson, Emma
Prabhakara, Karthik
Xue, Hasen
Smith, Philippa
Uray, Karen
Olson, Scott D.
Mays, Robert W.
Cox, Charles S.
Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title_full Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title_fullStr Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title_full_unstemmed Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title_short Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
title_sort therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856201/
https://www.ncbi.nlm.nih.gov/pubmed/29548333
http://dx.doi.org/10.1186/s12974-018-1122-8
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