Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest Yongchao Wang, MD, Tianxiang Gu, MD, PhD, Enyi.

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Inhibition of miR-29c Protects the Brain in a Rat Model of Prolonged Hypothermic Circulatory Arrest Tianxiang Gu MD, PhD Department of Cardiac Surgery.

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Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest Yongchao Wang, MD, Tianxiang Gu, MD, PhD, Enyi Shi, MD, PhD, Lei Yu, MD, Chun Wang, MD, PhD, Yuhai Zhang, MD, PhD, Qin Fang, MD The Journal of Thoracic and Cardiovascular Surgery Volume 150, Issue 3, Pages 675-684.e1 (September 2015) DOI: 10.1016/j.jtcvs.2015.04.062 Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Experimental groups and protocol. CPB, Cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; TU, transfection unit. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A-F, Vestibulomotor function assessed by the beam balance task after the surgical procedure. n = 8, for each of the 4 groups. *P < .01 versus sham group. #P < .05 versus DHCA group. DHCA, Deep hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 A-C, Cognitive function assessed by modified hole board test after the surgical procedure. n = 8, for each of the 4 groups. *P < .05 versus sham group. #P < .05 versus DHCA group. DHCA, Deep hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 MDA contents in the hippocampus. n = 4, for each of the 4 groups. *P < .05 versus sham group. #P < .05 versus DHCA group. DHCA, Deep hypothermic circulatory arrest; MDA, malondialdehyde. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 miR-29c expression in the hippocampus. n = 4, for each of the 4 groups. *P < .05 versus DHCA group. DHCA, Deep hypothermic circulatory arrest; miR-29c, microRNA-29c. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Results of Western blot. A and B, Representative Western blot pictures showing PGC-1α or caspase-3 expressions. C and D, Densitometric quantification of PGC-1α or caspase-3 expressions (folds to the sham group). n = 4, for each of the 4 groups. *P < .01 versus sham group. #P < .01 versus DHCA group. DHCA, Deep hypothermic circulatory arrest; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 7 Histologic examination. A, Representative coronal brain sections of the hippocampus and cerebellar vermis stained with hematoxylin–eosin; a, b, c, d, magnification of 40×; e, f, g, h, magnification of 200×; i, j, k, l, magnification of 400×; a, e, i, sham group; b, f, j, DHCA group; c, g, k, DHCA + vector group; d, h, i, DHCA + antagomiR-29c group. B, Pathologic scores. n = 8, for each of the 4 groups. *P < .05 versus DHCA group. DHCA, Deep hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Inhibition of miR-29c attenuates neurologic dysfunction after DHCA. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 675-684.e1DOI: (10.1016/j.jtcvs.2015.04.062) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions