title: Thromboxane A2 receptor antagonist SQ29548 reduces ischemic stroke-induced microglia/macrophages activation and enrichment, and ameliorates brain injury.
abstract: Thromboxane A2 receptor (TXA2R) activation is thought to be involved in thrombosis/hemostasis and inflammation responses. We have previously shown that TXA2R antagonist SQ29548 attenuates BV2 microglia activation by suppression of ERK pathway, but its effect is not tested in vivo. The present study aims to explore the role of TXA2R on microglia/macrophages activation after ischemia/reperfusion brain injury in mice. Adult male ICR mice underwent 90-min transient middle cerebral artery occlusion (tMCAO). Immediately and 24 h after reperfusion, SQ29548 was administered twice to the ipsilateral ventricle (10 μl, 2.6 μmol/ml, per dose). Cerebral infarction volume, inflammatory cytokines release and microglia/macrophages activation were measured using the cresyl violet method, quantitative polymerase chain reaction (qPCR), and immunofluorescence double staining, respectively. Expression of TXA2R was significantly increased in the ipsilateral brain tissue after ischemia/reperfusion, which was also found to co-localize with activated microglia/macrophages in the infarct area. Administration of SQ29548 inhibited microglia/macrophages activation and enrichment, including both M1 and M2 phenotypes, and attenuated ischemia-induced IL-1ß, IL-6, and TNF-α up-regulation and iNOS release. TXA2R antagonist SQ29548 inhibited ischemia-induced inflammatory response and furthermore reduced microglia/macrophages activation and ischemic/reperfusion brain injury.
authors: Department of Neurology &Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University, 200025, China.
authors: Aijuan
authors: A
authors: Yan
authors: School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Tingting
authors: T
authors: Zhang
authors: School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Xiao
authors: X
authors: Yang
authors: School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Jiaxiang
authors: J
authors: Shao
authors: Zhiyuan College, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors: Ningzhen
authors: N
authors: Fu
authors: Department of Neurology &Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University, 200025, China.
authors: Fanxia
authors: F
authors: Shen
authors: Department of Neurology &Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University, 200025, China.
authors: Yi
authors: Y
authors: Fu
authors: School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
authors: Weiliang
authors: W
authors: Xia
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated; D005911:Gliosis / Q000517:prevention & control*; D006834:Hydrazines / Q000008:administration & dosage* / Q000494:pharmacology; D008262:Macrophage Activation; D008813:Mice, Inbred ICR; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020521:Stroke / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C045749:SQ 29548