Figure 1 Effects of resveratrol on brain injury in middle cerebral artery occlusion rats
Note：A， Evans blue （EB） content of rat brains in each group； B， TTC staining results of rat brains in each group； C， Calculation of the proportion of cerebral infarction volume in each group of rat brains. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. n=5； compared with Sham group， ^***P<0.001； compared with MCAO group， ^##P<0.01； compared with Res group， ^&P<0.05.

Figure 2 Effects of resveratrol on neuronal damage in the brain tissue of middle cerebral artery occlusion rats
Note： Results of HE staining （A） and Nissl staining （B） of rat brain tissues in each group. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. n=5， scale bar = 20 μm.

Figure 3 Effects of resveratrol on pro-inflammatory cytokines in peripheral blood of rats with middle cerebral artery occlusion
Note： ELISA test results of IL-1β（A）， TNF-α（B） and CCL3（C） in rat serum. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. IL-1β， interleukin 1β； TNF-α， tumor necrosis factor-α； CCL3， C-C motif chemokine ligand 3. n=20； compared with Sham group， ^*P<0.05， ^***P<0.001； compared with MCAO group， ^#P<0.05， ^##P<0.01； compared with Res group， ^&P<0.05.

Figure 4 Effects of resveratrol on microglial activation in rats with middle cerebral artery occlusion
Note： Immunofluorescence detection （A） and quantitative analysis of fluorescence intensity （B-C） of Iba-1 and CCR5 in rat brain tissue. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. Iba-1， ionized calcium-binding adapter molecule 1； CCR5， C-C motif chemokine receptor 5. Scale bar=50 μm； n=5； compared with Sham group， ^***P<0.001； compared with MCAO group， ^##P<0.01； compared with Res group， ^&P<0.05， ^&&P<0.01.

Figure 5 Effects of resveratrol treatment on CCL3/CCR5 signaling pathway and blood-brain barrier-related proteins in brain tissues of rats with middle cerebral artery occlusion
Note： A-B， Western blotting results and quantitative analysis of CCR5 and CCL3 proteins in rat brain tissue； C-D， Western blotting results and quantitative analysis of p-NF-κB， NF-κB， MMP9， and occludin proteins in rat brain tissue. CCR5， C-C motif chemokine receptor 5； CCL3， C-C motif chemokine ligand 3； p-NF-κB， phosphorylated nuclear factor-κB； NF-κB， nuclear factor-κB； MMP9， matrix metalloproteinase 9； occludin， tight junction protein. The MCAO, Res, Res+Agonist, and Res+Antagonist groups were subjected to middle cerebral artery occlusion (MCAO) for 45 min followed by reperfusion to establish the rat model of cerebral ischemia, while the Sham group underwent carotid artery exposure without ischemia. After reperfusion, resveratrol (60 mg/kg) was intraperitoneally injected in Res, Res+Agonist and Res+Antagonist groups, and an equal volume of normal saline was injected in Sham and MCAO groups. Thirty minutes later, CCR5 agonist (20 μg/kg) was injected via the tail vein in the Res+Agonist group, CCR5 inhibitor (1 mg/kg) was injected via the tail vein in the Res+Antagonist group, and the equal volume of normal saline was injected via the tail vein in the Res, Sham and MCAO groups. Thereafter, resveratrol, CCR5 agonist, CCR5 inhibitor, or saline were administered every 24 hours for 3 consecutive days. n=5； compared with Sham group， ^***P<0.001； compared with MCAO group， ^#P<0.05， ^##P<0.01； compared with Res group， ^&P<0.05.