Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage

Author:

Chang Che-Feng12,Massey Jordan2,Osherov Artem2,Angenendt da Costa Luís Henrique3,Sansing Lauren H.2

Affiliation:

1. From the Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei (C.-F.C.)

2. Department of Neurology, Yale University School of Medicine, New Haven, CT (C.-F.C., J.M., A.O., L.H.S.)

3. Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Brazil (L.H.A.d.C.).

Abstract

Background and Purpose— Enhancement of erythrophagocytosis by macrophages in a timely manner can limit the toxic effects of erythrocyte metabolites and promote brain recovery after intracerebral hemorrhage (ICH). In the current study, we investigated the therapeutic effect of retinoid X receptor agonist, bexarotene, in facilitating erythrophagocytosis and neurobehavioral recovery in 2 mouse models of ICH. Methods— Bone marrow-derived macrophages and fluorescently labeled erythrocytes were used to study erythrophagocytosis in vitro with phenotypic changes quantified by gene expression. ICH was modeled in vivo using intrastriatal autologous blood and collagenase injection in mice with and without bexarotene treatment beginning 3 hours after ICH. In vivo phagocytosis, ability and hematoma clearance were evaluated by erythrophagocytosis assays, flow cytometry, and histological analysis. Neurological deficits and functional recovery were also quantified. Results— Bexarotene increased macrophage expression of phagocytosis receptors and erythrophagocytosis and reduced macrophage TNF (tumor necrosis factor) production in vitro. In vivo, bexarotene treatment enhanced erythrophagocytosis, reduced hematoma volume, and ultimately improved neurological recovery after ICH in 2 distinct models of ICH. Conclusions— Bexarotene administration is beneficial for recovery after ICH by enhancing hemorrhage phagocytosis, modulating macrophage phenotype, and improving functional recovery.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Clinical Neurology

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