Dynamics of inflammatory immune response in a mouse model of traumatic spinal cord injury

M. Hassanpour Golakani, M. G. Mohammad, H. Li, S. N. Breit, M. Ruitenberg, D. A. Brown

Research output: Chapter in Book / Conference PaperConference Paper

Abstract

![CDATA[Inflammatory responses post spinal cord injury (SCI) may be detrimental or beneficial. However, the dynamics of this inflammatory response are largely unknown. The aim of this study was to quantify and characterize immune cells in, and around, the injury site, as well as their relationship with locomotor functional recovery after contusive SCI. Mice had a 70 kilo dyne force SCI induced using the Horizon impactor after laminectomy. Locomotor function was assessed, using the Basso Mouse Scale (BMS). At days 7, 14, 21, and 28 post injury, the entire spinal cord was removed and mononuclear cells associated with SCI were isolated. Various immune cell populations were characterized and quantified using multiparameter flow cytometry. Results were validated using both IHC and IF staining and correlated with histological assessment of injury parameters and injury course. Post SCI mice had complete paralysis, with functional recovery to score 3-4 over 28 days post injury (dpi). Smaller mice had significantly less recovery. Peripherally derived immune cells progressively increased over the course of recovery from SCI, most of which were T-cells. Both CD4+ and CD8+ T-cells increased by 4-5 fold at day 28 compared to day 7 dpi. The CD4+ T-cell population was predominantly INFγ+ (Th1), with FoxP3+ (T-regulatory) and IL17+ (Th17) cells being less frequent. Myeloid DCs (mDCs) were the predominant subtype of DCs present. They increased significantly from day 21 to 28 dpi. On the other hand, CD8α+ DCs were the least frequent DC subtypes and significantly decreased by about 3 fold at day 21 and then increased at 28 dpi. Plasmacytoid DC (pDC) frequency was unchanged from 7 dpi. There were also no significant changes in macrophages and B cells over 7-28 dpi, indicating early recruitment. Immunohistology revealed CD11c+ cells and CD3+ T-cells were predominantly confined to the injury core. While GFAP+ astrocytes surrounded the core. Iba-1+ microglia were dispersed throughout the entire spinal cord. White mater surrounding the injury core was substantially demyelinated and myelin was observed in injury core. Functional recovery was positively correlated with the total numbers of injury-associated macrophages and their percentage of CD45+ cells at 28 dpi. Improved recovery was also positively correlated with CD11c+ DCs’ percentage of CD45+ cells, mostly consisting of mDCs. On the other hand, pDC numbers were negatively correlated with functional recovery. The changes for T-cells and their subtypes were not significantly related to improvement. These data suggest a role for DCs and macrophages in the resolution of SCI and identify them as a potential therapeutic target.]]
Original languageEnglish
Title of host publicationAbstracts Book of the 2105 Society for Neuroscience Annual Meeting, Chicago, Illinois, U.S.A., October 17-21 2015
PublisherSociety for Neuroscience
Number of pages1
Publication statusPublished - 2015
EventSociety for Neuroscience. Annual Meeting -
Duration: 1 Jan 2017 → …

Conference

ConferenceSociety for Neuroscience. Annual Meeting
Period1/01/17 → …

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