title: CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling.
abstract: Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic deficits. CD36 expression in perihematomal tissues in wild-type mice following ICH was increased, whereas the hematoma absorption in CD36(-/-) mice was decreased. CD36(-/-) mice also showed aggravated neurologic deficits and increased TNF-α and IL-1β expression levels. The phagocytic capacity of CD36(-/-) microglia for RBCs was also decreased. Additionally, the CD36 expression in the perihematoma area after ICH in TLR4(-/-) and MyD88(-/-) mice was significantly increased, and hematoma absorption was significantly promoted, which was significantly inhibited by an anti-CD36 Ab. In vitro, TNF-α and IL-1β significantly inhibited the microglia expression of CD36 and reduced the microglia phagocytosis of RBCs. Finally, the TLR4 inhibitor TAK-242 upregulated CD36 expression in microglia, promoted hematoma absorption, increased catalase expression, and decreased the H2O2 content. These results suggested that CD36 mediated hematoma absorption after ICH, and TLR4 signaling inhibited CD36 expression to slow hematoma absorption. TLR4 inhibition could promote hematoma absorption and significantly improve neurologic deficits following ICH.
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
authors.forename: Huang
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu 610083, China; and Department of Histoembryology and Neurobiology, Chengdu Medical College, Chengdu 610083, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
authors.forename: PengFei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
authors.forename: YanChun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
authors.forename: XiaoYi
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; yangqwmlys@hotmail.com.
authors.forename: QingWu
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001791:Blood Platelet Disorders / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020201:Brain Hemorrhage, Traumatic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology*; D002374:Catalase / Q000235:genetics / Q000276:immunology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006407:Hematoma, Epidural, Cranial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000276:immunology; D008297:Male; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D018955:CD36 Antigens; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006861:Hydrogen Peroxide; D002374:Catalase