Inhibition of TIM-4 protects against cerebral ischaemia-reperfusion injury

Abstract

TIM-4 plays an important role in ischaemia-reperfusion injury of liver and kidney; however, the effects of TIM-4 on cerebral ischaemia-reperfusion injury (IRI) are unknown. The purpose of the present study was to investigate the potential role of TIM-4 in experimental brain ischaemia-reperfusion injury. In this study, cerebral ischaemia reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 1 hour in C57/BL6 mice. The TIM-4 expression was detected in vivo or vitro by real-time quantitative polymerase chain reaction, Western blot and flow cytometric analysis. In vivo, the administration of anti-TIM-4 antibodies significantly suppressed apoptosis, inhibited inflammatory cells and enhanced anti-inflammatory responses. In vitro, activated microglia exhibited reduced cellular proliferation and induced IRI injury when co-cultured with neurons; these effects were inhibited by anti-TIM-4 antibody treatment. Similarly, microglia transfected with TIM-4 siRNA and stimulated by LPS + IFN-γ alleviated the TIM-4-mediated damage to neurons. Collectively, our data indicate that the inhibition of TIM-4 can improve the inflammatory response and exerts a protective effect in cerebral ischaemia-reperfusion injury.