Figure 1.

IGF‐1 deficiency exacerbates hypertension (HT)‐induced CMHs in mice. (A) Adeno‐associated viral knockdown of hepatic Ifg1 (Igf1 ^f/f + TBG‐Cre‐AAV8) significantly decreases the levels of circulating IGF‐1 compared to control animals. Data are mean ± SEM. *P = 0.001 vs. control (t‐test). (B) Treatment with angiotensin II plus l‐NAME elicited similar increases in systolic blood pressure in control and IGF‐1‐deficient mice. *P < 0.05 vs. control normotensive (one‐way ANOVA, Tukey's post hoc test). (C) Cumulative incidence curves for neurological signs of hypertension‐induced intracerebral hemorrhage in control (n = 24) and IGF‐1‐deficient mice (n = 31). In IGF‐1‐deficient mice, there was a significant increase in CMH incidence compared to control mice (log‐rank test; Mantel‐Cox). (D–G) Representative images of CMHs stained by diaminobenzidine in the cortex, brain stem, white matter, and cerebellum of hypertensive IGF‐1‐deficient mice. (H–K) Black arrows point to cerebral intraparenchymal arterioles in close proximity to the hemorrhages. Hemorrhages were often confined to and spread along the perivascular spaces (arrowheads). Note in (K) the spread of the hemorrhage to the daughter branches of an arteriole along the perivascular spaces. (L): Total number of hypertension‐induced CMHs throughout the entire brain of control and IGF‐1‐deficient mice. Data are mean ± SEM. *P < 0.05 (t‐test). (M) The pie charts illustrate the similar distribution of CMHs by location in both experimental groups. (N) The cumulative frequency distribution of CMHs by volume significantly shifts to the left in IGF‐1‐deficient mice compared to control, indicating that IGF‐1 deficiency specifically increases the number of smaller bleeds. The maximum difference between the cumulative distributions was calculated using the two‐sample Kolmogorov–Smirnov test (D: 0.5202; P < 0.0001).