Spiess, D. A., Campos, R. M. P., Conde, L., Didwischus, N., Boltze, Johannes, Mendez-Otero, R. and Pimentel-Coelho, P. M. (2022) Subacute AMD3100 treatment is not efficient in neonatal hypoxic-schemic rats. Stroke, 53 (2). pp. 586-594. doi:10.1161/STROKEAHA.120.033768 ISSN 0039-2499.

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Abstract

Background and Purpose:
Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE.

Methods:
P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively.

Results:
AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment.

Conclusions:
These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model.

Item Type:	Journal Article
Alternative Title:
Subjects:	Q Science > QP Physiology R Medicine > RB Pathology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Ischemia, Cerebrovascular disease , Anoxemia , Injections, Hypodermic, Hematopoietic stem cells
Journal or Publication Title:	Stroke
Publisher:	Lippincott Williams & Wilkins
ISSN:	0039-2499
Official Date:	February 2022
Dates:	Date Event February 2022 Published 19 November 2021 Available 27 October 2021 Accepted
Volume:	53
Number:	2
Page Range:	pp. 586-594
DOI:	10.1161/STROKEAHA.120.033768
Status:	Peer Reviewed
Publication Status:	Published
Reuse Statement (publisher, data, author rights):	This is a non-final version of an article published in final form in Spiess, D. A., Campos, R. M. P., Conde, L., Didwischus, N., Boltze, Johannes, Mendez-Otero, R. and Pimentel-Coelho, P. M. (2022) Subacute AMD3100 treatment is not efficient in neonatal hypoxic-schemic rats. Stroke, 53 (2). pp. 586-594. doi:10.1161/STROKEAHA.120.033768
Access rights to Published version:	Restricted or Subscription Access
Copyright Holders:	© 2021 American Heart Association, Inc.
Date of first compliant deposit:	9 November 2021
Date of first compliant Open Access:	19 May 2022
Related URLs:	Publisher

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