Neuroscience Correction for “The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice,” by Huilin Yu, Haiyu Luo, Luping Chang, Shisheng Wang, Xue Geng, Lijing Kang, Yi Zhong, Yongliang Cao, Ranran Wang, Xing Yang, Yuanbo Zhu, Mei-Juan Shi, Yue Hu, Zhongwang Liu, Xuhui Yin, Yunwei Ran, Hao Yang, Wenying Fan, and Bing-Qiao Zhao, which published January 31, 2022; 10.1073/pnas.2111896119 (Proc. Natl. Acad. Sci. U.S.A. 119, e2111896119).
The authors note that Fig. 3 appeared incorrectly. The incorrect image was erroneously included for the MLN4924 24h panel in Fig. 3C during figure assembly. The corrected figure and its legend appear below. The online version has been corrected.
Fig. 3.
MLN4924 attenuates BBB breakdown after ischemic stroke. (A and B) Representative images and quantification of Evans blue extravasation 24 h after stroke in mice treated with vehicle or MLN4924 (n = 8). (C) Representative in vivo multiphoton microscopic images of intravenously injected FITC-dextran (MW = 40 KDa) leakage from cortical vessels in sham-operated mice and ischemic mice treated with vehicle or MLN4924 24 and 48 h after stroke. (Scale bar, 100 μm.) (D) Quantification of the permeability (P) product of FITC-dextran for each group (n = 6). (E) Representative images of coronal brain sections showing the leakage of intravenously injected BSA into the brain. (Scale bar, 1 mm.) (F) Quantification of extravascular BSA fluorescence (n = 8). (G) Western blot assay for IgG levels in capillary-depleted brain tissue. (H) Quantification of IgG deposits in capillary-depleted brain tissue (n = 8). (I) Representative images and quantitation of IgG perivascular accumulation (green) in sham-operated mice and ischemic mice treated with vehicle or MLN4924 24 and 48 h after stroke. Capillaries were stained with CD31 (white). (Scale bar, 10 μm.) (J) Quantitation of IgG perivascular accumulation (n = 8). (K–O) Reduced tight junction protein ZO-1, occludin, and claudin-5 and adherens junction protein VE-cadherin levels in isolated brain microvessels of ischemic mice and reversal by MLN4924 treatment (n = 8). (P) Immunohistochemical quantification of TUNEL-positive endothelial cells in sham-operated mice and ischemic mice treated with vehicle or MLN4924 24 h after stroke (n = 8). Data were analyzed using unpaired Student’s t test or one-way ANOVA followed by Bonferroni multiple comparison test. Values are mean ± SD. *P < 0.05. HPF, high-power field.
The authors note that Fig. 4 appeared incorrectly. The image of the β-actin panel in Fig. 4G was inadvertently duplicated from Fig. 3K during figure compilation. The corrected figure and its legend appear below. The online version has been corrected.
Fig. 4.
MLN4924 reduces neutrophil infiltration and proinflammatory cytokines expression in the ischemic brains. (A) Timeline of multiphoton microscopic experiments. (B) Representative in vivo multiphoton microscopic images of rolling and adherent neutrophils (red) inside the blood vessels (green) and of infiltrated neutrophils into the brain parenchyma. (Scale bar, 40 μm.) (C–E) Number of adherent neutrophils and transmigrated neutrophils and rolling velocity in sham-operated mice and ischemic mice treated with vehicle or MLN4924 12 h after stroke (n = 6). (F) Quantification of Ly6G+ neutrophils at 6, 12, 24, and 48 h (n = 8). HPF, high-power field. (G and H) Representative Western blot and quantification of the amount of neutrophils in the ischemic brain in mice treated with vehicle or MLN4924 at 24 h (n = 8). (I) Quantification of MPO activity at 24 h (n = 8). (J–M) Relative gene expression of CXCL1, CX3CL1, CCL2, and CCR1 in the ischemic brains of mice at 24 h (n = 8). (N–P) Quantification of proinflammatory cytokines IL-6, IL-1β, and TNF-α by enzyme-linked immunoassay (ELISA) at 24 h (n = 8). (Q and R) Quantification of the number of activated microglia cells and monocytes/macrophages in the ischemic brains of mice at 24 h (n = 8). (S and T) Representative images and quantification of DHE staining reflected the ROS levels in the brains of mice at 24 h (n = 8). (Scale bar, 40 μm.) Data were analyzed using one-way ANOVA followed by Bonferroni multiple comparison test. Values are mean ± SD. *P < 0.05. NS, not significant.
The authors note that Supporting Fig. 3 in the SI Appendix appeared incorrectly. In Fig. S3, the image of MLN4924 24h panel in Fig. S3A is incorrect and partially overlaps with the image of MLN4924+Ad-shNF1+anti-ICAM-1 ab panel in Fig. 6P. This wrong image was accidently misapplied during figure assembly. The SI Appendix has been corrected online.
Authors assert that the errors do not affect the scientific results of the paper.