Fig. 1: Ischaemic events induce recurrent stroke and exacerbate plaque vulnerability.

a, Recurrence rates by incident stroke aetiology in the first month (days 0–30) and months 2–12 (days 31–360) in a population of 1,798 patients with stroke (log-rank test in Kaplan–Meier curves; Extended Data Fig. 1a). b, Experimental design. Eight-week-old high-cholesterol diet (HCD)-fed ApoE^−/− mice underwent tandem stenosis (TS) surgery, and stroke or sham surgery 4 weeks later. The recurrence of secondary ischaemia in the contralateral hemisphere was examined by MRI and histological analysis. c, Representative MRI image (the white dashed line denotes the primary stroke area; the red dashed line indicates recurrent contralateral stroke). Fluoro Jade C (FJC; lower left panel) staining corresponding to MRI. Scale bars, 3 mm. Representative images of histological stainings (FJC, TUNEL and Iba-1) from control mice or mice with a secondary lesion (middle panels). Scale bars, 50 μm. Pie charts for stroke recurrence 7 days after sham or stroke surgery (n = 24 (sham) and n = 40 (stroke); red denotes with secondary lesion, and grey indicates without secondary lesion) are also shown (right panels). d, Representative images of a plaque rupture (the arrowheads in the Sirius red and collagen I stainings) with contiguous CCA thrombus stained for von Willebrand factor (vWF) and platelets (CD41). Chi-squared test (P < 0.0001) for occurrence of CCA thrombi and secondary brain lesions (n = 12 per group). Scale bars, 50 µm. e, Quantification of plaque vulnerability in CCA sections 7 days after sham or stroke surgery (analysis of variance (ANOVA); n = 9–10 per group). f, Experimental design as shown in panel b, but with induction of myocardial infarction (MI) instead of stroke (left), and quantification of plaque vulnerability (right; U-test; n = 5–6 per group). g,h, Experimental design and representative FACS plots (g) for quantification (h) of infiltrated leukocytes and Ly6C^high and CCR2⁺ monocyte subpopulations in CCA 24 h after sham or stroke surgery (U-test; n = 6 per group). i.v., intravenous. i, Representative images (left) and quantification (right) of proliferating macrophages (ANOVA; n = 8–10 per group). Scale bars, 50 μm. e,f,h,i, Bars indicate the mean.