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: Aijuan Yan, Tingting Zhang, Xiao Yang, Jiaxiang Shao, Ningzhen Fu, Fanxia Shen, Yi Fu, Weiliang Xia
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 35885 (10 24 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27775054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Cytokines
• Fatty Acids, Unsaturated
• Hydrazines
• Receptors, Thromboxane A2, Prostaglandin H2
• SQ 29548

Topics

• Animals
• Bridged Bicyclo Compounds, Heterocyclic
• Cytokines (analysis)
• Disease Models, Animal
• Fatty Acids, Unsaturated
• Gliosis (prevention & control)
• Hydrazines (administration & dosage, pharmacology)
• Macrophage Activation
• Mice, Inbred ICR
• Receptors, Thromboxane A2, Prostaglandin H2 (antagonists & inhibitors)
• Reperfusion Injury (pathology, prevention & control)
• Stroke (complications, drug therapy, pathology)
• Treatment Outcome