Hyperglycemia and PPARγ Antagonistically Influence Macrophage Polarization and Infarct Healing After Ischemic Stroke

Stroke; a Journal of Cerebral Circulation
Michael GliemSebastian Jander

Abstract

Secondary intracerebral hemorrhage (sICH) is a potentially serious complication of ischemic stroke, in particular under concomitant oral anticoagulation. Previous studies in murine stroke models defined a novel vascular repair function of hematogenous monocytes/macrophages (MO/MP), which proved essential for the prevention of oral anticoagulation-associated sICH. Here, we addressed the question whether hyperglycemia as a clinically relevant prohemorrhagic risk factor and peroxisome proliferator-activated receptor gamma (PPARγ) activation affect MO/MP differentiation and the risk of sICH after ischemic stroke. Oral anticoagulation-associated sICH was induced by phenprocoumon feeding to mice undergoing transient middle cerebral artery occlusion. Hyperglycemia was induced by streptozotocin treatment. The role of PPARγ-dependent MO/MP differentiation was addressed in mice with myeloid cell-specific PPARγ-knockout (LysM-PPARγ(KO)). Pharmacological PPARγ activation via pioglitazone was tested as a treatment option. Hyperglycemic mice and normoglycemic LysM-PPARγ(KO) mice exhibited abnormal proinflammatory skewing of their hematogenous MO/MP response and abnormal vascular remodeling in the infarct border zone, leading to an increased ...Continue Reading

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Citations

Nov 21, 2015·Biochimica Et Biophysica Acta·Michael GliemSebastian Jander
Dec 15, 2015·Current Opinion in Pharmacology·Diana Amantea, Giacinto Bagetta
Aug 25, 2016·Drug Discovery Today·Urmi PatelJohnson Rajasingh
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Sep 20, 2019·Journal of Immunology Research·Jing-Jing SunHui Li
Aug 11, 2020·Journal of Neuroscience Research·Marcin GamdzykJohn H Zhang
Oct 21, 2016·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Nikunj Satani, Sean I Savitz
May 12, 2018·Stroke; a Journal of Cerebral Circulation·Masakazu KotodaTomoki Hashimoto
Oct 17, 2020·Experimental Neurology·Eunhee Kim, Sunghee Cho
May 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nannan LiuGuanhua Du

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