Comparative Efficacy of Remote Ischemic Conditioning and Hypothermia in Permanent and Transient Cerebral Ischemia in Male Mice

Abstract

Remote ischemic conditioning (RIC) has attracted considerable attention as a brain protection strategy, although its impact remains unclear. Hypothermia is the most effective strategy in experimental transient cerebral ischemia. Therefore, we compared the efficacy of RIC, hypothermia, and no treatment on cerebral ischemia. We assessed the effects of both permanent and transient middle cerebral artery occlusion (MCAO) for 45 min in male mice. Brain hemodynamics were monitored during and after the procedure via 2D color-coded ultrasound imaging. Ischemic lesions on magnetic resonance imaging (MRI)–diffusion-weighted imaging (DWI), early breakdown of microtubule-associated protein 2 (MAP2), expression levels of inflammatory cytokines by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and neurological signs and infarct volume were examined. In permanent MCAO, RIC increased cerebral blood flow (CBF) in the peri-infarct area, reduced early lesions on MRI–DWI, decreased early MAP2 breakdown, and lowered infarct volume compared with no treatment. However, hypothermia only showed a protective effect against neurological signs. In contrast, in transient MCAO, both RIC and hypothermia reduced the expression of inflammatory cytokines, mitigated MAP2 breakdown, and reduced infarct volume to a similar extent compared with no treatment. In conclusion, although RIC proved to be more effective than hypothermia in permanent MCAO, the protective effects of RIC and hypothermia were comparable in transient cerebral ischemia. Thus, RIC could be a promising strategy for brain protection against cerebral ischemia.