Abstract 182: Rxrα in Microglia Acts as Central Player in the Cleanup and Repair After Ischemic Stroke

• DOI: 10.1161/str.49.suppl_1.182
• Publication Date: 2018-10-08T17:54:39Z
• Authors: Shun-Ming Ting; Xiurong Zhao; Guanghua Sun; Juan J Garrido; Lidiya Obertas; Jaroslaw Aronowski
• Keywords: Retinoid X receptor; Bexarotene

Microglia/macrophage (MΦ) are immune response cells with function in clearing cell debris and tissue repair after ischemic brain damage. Retinoid X receptor alpha (RXRα) is a pleiotropic transcription factor regulating differentiation, lipid/glucose metabolism responses, including MΦ. Studies from this lab suggest that the dimerization of RXRα peroxisome proliferator-activated γ (PPARγ) to form transcriptionally active structure plays critical roles enhancing MΦ polarization toward “healing” phenotype. All studies were performed applying scientific rigor. First, we showed treatment microglia culture selective agonist RXRα, bexarotene (BEX), promotes microglia’ “beneficial” phenotype enhancement phagocytic functions engulfment dead neurons. Next, BEX (5mg/kg, i.p.) given daily rats thromboembolic stroke reduced infarct volume at d7. The neurological deficit was by d7, but not d3 stroke. This beneficial effects takes place during sub-acute phase post-stroke. To further investigate role ischemia, generated macrophage-targeting knockout mice (MacRXRα -/- ) crossing Lyz-Cre flox/flox mice. We subjected MacRXRα (control) 60 min MCA/CCA reversible occlusion. 24h later received (5mg/kg once day for 7 days, or vehicle. conducted behavioral evaluations 28 days. showed, agreement rat data, control receiving significant improvement long-term recovery had atrophy d28 also effect significantly mice, as compared Limitation: Since may have deficiency neutrophils, now conducting parallel evaluate neutrophils. Our study suggests play important coordinating cleanup post-stroke phase. Also, has uniquely long therapeutic window.