Remote ischemic preconditioning protects against ischemic stroke in streptozotocin-induced diabetic mice via anti-inflammatory response and anti-apoptosis.

ABSTRACT

OBJECTIVE: It has been shown that remote ischemic preconditioning (RIPreC) attenuates ischemic injury after stroke in healthy rats or mice. The present study aims to examine whether RIPreC offers neuroprotection against ischemic stroke in streptozotocin-induced diabetic mice. METHODS: Streptozotocin (STZ, 120 mg/kg) was intraperitoneally injected into the mice to induce type 1 diabetic model. The immune and inflammatory changes were analyzed 2 days after reperfusion by flow cytometry and multiplex cytokine assay analysis, respectively. RESULTS: We found that RIPreC reduced infarct sizes and alleviated neurological impairment in diabetic mice. RIPreC decreased CD8 T cells infiltrated into the brain, and attenuated the decreases of CD8 T cells in the blood, CD4 T cells and CD8 T cells in the spleen. Results from multiplex cytokine assay showed that RIPreC treatment decreased IL-6, IL-1 beta and TNF alpha levels in the cortex, while it inhibited IL-6 level in the hippocampus and striatum, and TNF alpha level in the hippocampus. RIPreC treatment also downregulated IL-6 and IFN gamma level in the blood, which increased after cerebral ischemic injury. In addition, RIPreC reduced pro-apoptotic protein BAX expression in the ischemic brain. CONCLUSIONS: Our results indicate that RIPreC attenuates cerebral injuries in streptozotocin-induced diabetic mice via anti-inflammatory response and anti-apoptosis in the ischemic brain.