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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

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

Authors: Supinder S. Bedi, Benjamin M. Aertker, George P. Liao, Henry W. Caplan, Deepa Bhattarai, Fanni Mandy, Franciska Mandy, Luis G. Fernandez, Pamela Zelnick, Matthew B. Mitchell, Walter Schiffer, Margaret Johnson, Emma Denson, Karthik Prabhakara, Hasen Xue, Philippa Smith, Karen Uray, Scott D. Olson, Robert W. Mays, Charles S. Cox Jr

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

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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Metadata
Title
Therapeutic time window of multipotent adult progenitor therapy after traumatic brain injury
Authors
Supinder S. Bedi
Benjamin M. Aertker
George P. Liao
Henry W. Caplan
Deepa Bhattarai
Fanni Mandy
Franciska Mandy
Luis G. Fernandez
Pamela Zelnick
Matthew B. Mitchell
Walter Schiffer
Margaret Johnson
Emma Denson
Karthik Prabhakara
Hasen Xue
Philippa Smith
Karen Uray
Scott D. Olson
Robert W. Mays
Charles S. Cox Jr
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1122-8

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