Remote Limb Ischemic Conditioning during Cerebral Ischemia Reduces Infarct Size through Enhanced Collateral Circulation in Murine Focal Cerebral Ischemia

Background: Remote ischemic conditioning (RIC) induces protection in focal cerebral ischemia. The conditioning is divided into pre-, per-, and postconditioning. However, the mechanisms of RIC remain unknown. Objectives: This study aimed to determine the most effective subtype of RIC. We also examined involvement of collateral circulation on RIC. Methods: Transient middle cerebral artery occlusion (MCAO) was performed with nylon sutures in adult C57BL/6 mice under the monitoring of cerebral blood flow (CBF). Fifty mice were divided into 5 groups: MCAO control group, delayed pre-RIC group (RIC 24 hours before MCAO), early pre-RIC group (RIC 5 minutes before MCAO), per-RIC group (RIC during MCAO), and post-RIC group (RIC 5 minutes after MCAO). In other middle cerebral artery (MCA) control and per-RIC groups, collateral circulation was visualized with latex compound perfusion. Results: After MCAO, CBF was reduced by 80% in all groups. At the end of MCAO, relative increase in CBF in per-RIC group was significantly greater than that in MCA control, whereas the infarct volume in per-RIC group was significantly smaller than that in other groups. The diameter of leptomeningeal anastomosis was larger in the per-RIC group than that in the control group. Conclusions: Among the 4 RIC procedures, only the per-RIC group showed clear brain protection. Enhancement of collateral circulation could play a role in the protective effect of per-RIC.