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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24702

Title: The use of a specific HDAC3 inhibitor to modulate macrophage polarization in order to improve functional recovery after spinal cord injury
Authors: Baeten, Paulien
Advisors: HENDRIX, Sven
Issue Date: 2017
Publisher: tUL
Abstract: Macrophages play an important role during the neuroinflammatory response of spinal cord injury (SCI). The dominant M1 macrophages induce axonal retraction while the transient M2 macrophages induce regeneration. Histone deacetylase 3 (HDAC3) influences the macrophage polarization; inhibition of HDAC3 would shift the polarization towards the M2 phenotype. Therefore, the hypothesis of this study is that inhibition of HDAC3, as a central regulator of macrophage polarization, will improve functional recovery in a mouse model of SCI. In vitro analysis of several M1 and M2 markers reveals that HDAC3 specific inhibitor RGFP966 boosts the Arg1-correlated M2 phenotype. RGFP966 does not affect the LPS-induced gene expression of M1 markers. LPS- and IL-4-primed macrophages phagocytose spinal cord debris in vitro and become foamy as a result. Administration of RGFP966 reduces the formation of foamy macrophages in vitro regardless of their activation state. These in vitro results strengthen our hypothesis. However, RGFP966 does not improve functional recovery in the mouse model of SCI nor does it modulate the macrophage polarization on acute or on chronic term in vivo. This is possibly due to the complex pathophysiology which might overcome the potential effect of RGFP966.
Notes: Master of Biomedical Sciences-Clinical Molecular Sciences
URI: http://hdl.handle.net/1942/24702
Category: T2
Type: Theses and Dissertations
Appears in Collections: Master theses

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