Abstract
BACKGROUND AND PURPOSE: Impairment of macrophage polarization from a proinflammatory macrophage type 1 (M1) population to an anti-inflammatory macrophage type 2 (M2) population is a hallmark of poor wound healing. In this study, we aimed to evaluate the distribution of M1 and M2 macrophages and to analyze their association with healing in aneurysms embolized by endovascular coiling.
MATERIALS AND METHODS: Elastase-induced aneurysms were created in female rabbits and subsequently embolized with platinum coils. Aneurysm occlusions were evaluated with angiographic imaging at 1 (n = 6), 3 (n = 5), or 6 (n = 6) months. Aneurysm tissues were harvested for histologic analysis, quantification of M1 and M2 macrophages by immunofluorescence, and collagen deposition determined by Masson trichrome staining. Histologic grading of aneurysm healing was also performed. Untreated aneurysms were used as controls (n = 6).
RESULTS: The M1 macrophage population was highest at 1 month posttreatment, progressively decreasing at 3 and 6 months. The M2 macrophage population progressively increased at 3 and 6 months posttreatment. The highest collagen deposition was at 6 months posttreatment. We found a moderate-to-weak direct correlation between the percentage of M2 macrophages and collagen deposition, as well as total histologic scores overall, and a strongly positive direct correlation between the percentage of M2 macrophages and total histologic scores at 6 months posttreatment.
CONCLUSIONS: Our data support the direct correlation between M2 macrophage polarization and healing in aneurysm tissues. Our results show a positive relationship between M2 macrophage populations and total histologic scores at later stages of healing after endovascular coiling. We conclude that interventions aimed at stimulating M2 macrophage expression locally may improve aneurysm healing after coil embolization.
ABBREVIATIONS:
- CD80
- cluster of differentiation 80
- CD206
- cluster of differentiation 206
- M1
- macrophage type 1
- M2
- macrophage type 2
Footnotes
This study was supported by a grant from the National Institutes of Health (R01NS076491 and U01-NS089692) and, in part, by a fellowship award through the National Defense Science and Engineering Graduate Fellowship Program, sponsored by the Air Force Research Laboratory, the Office of Naval Research, and the Army Research Office.
Disclosures: Scott Herting—RELATED: Grant: Department of Defense, National Defense Science and Engineering Graduate Fellowship, Comments: The National Defense Science and Engineering Graduate fellowship supported me by providing tuition and stipends during graduate school. Duncan Maitland—RELATED: Grant: National Institutes of Health, Comments: National Institute of Neurological Disorders and Stroke, Grant/Award No.: U01-NS089692*; UNRELATED: Board Membership: Shape Memory Medical Inc, Comments: Shape Memory Medical Inc (shapemem.com) is commercializing neuorvascular and other vascular occlusion devices. These devices and Shape Memory Medical Inc were not involved in the work in this article. I am a cofounder and board member at Shape Memory Medical Inc; Patents (Planned, Pending or Issued): Texas A&M University and Lawrence Livermore National Laboratory, Comments: I have 40 issued patents and many pending related to vascular occlusion technology. None of the technology that I developed was part of this work; Royalties: Texas A&M University and Lawrence Livermore National Laboratory, Comments: I receive licensing royalty payments from the license of vascular occlusion technology by Shape Memory Medical Inc, paid to my former (Lawrence Livermore) and current (Texas A&M) employers. None of my licensed principal investigator was involved in this work; Stock/Stock Options: Shape Memory Medical Inc, Comments: I own stock and stock options in Shape Memory Medical Inc. Shape Memory Medical Inc was not involved in this article. David F. Kallmes—UNRELATED: Grants/Grants Pending: Medtronic, MicroVention, NeuroSigma, Neurogami, Comments: preclinical aneurysm research support.* Ram Kadirvel—RELATED: Grant: National Institutes of Health.* *Money paid to the Institution.
- © 2020 by American Journal of Neuroradiology
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