Comprehensive three-dimensional analysis (CUBIC-kidney) visualizes abnormal renal sympathetic nerves after ischemia/reperfusion injury

被引：37

作者：

Hasegawa, Sho ^{[1
]}

Susaki, Etsuo A. ^{[2
,3
,4
]}

Tanaka, Tetsuhiro ^{[1
]}

Komaba, Hirotaka ^{[5
,6
,7
]}

Wada, Takehiko ^{[5
]}

Fukagawa, Masafumi ^{[5
]}

Ueda, Hiroki R. ^{[2
,4
,8
]}

Nangaku, Masaomi ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Div Nephrol & Endocrinol, Tokyo, Japan

[2] Univ Tokyo, Dept Syst Pharmacol, Grad Sch Med, Tokyo, Japan

[3] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama, Japan

[4] RIKEN Ctr Biosyst Dynam Res, Lab Synthet Biol, Suita, Osaka, Japan

[5] Tokai Univ, Sch Med, Div Nephrol Endocrinol & Metab, Isehara, Kanagawa, Japan

[6] Tokai Univ, Interact Translat Res Ctr Kidney Dis, Sch Med, Isehara, Kanagawa, Japan

[7] Tokai Univ, Inst Med Sci, Isehara, Kanagawa, Japan

[8] Univ Tokyo, Int Res Ctr Neurointelligence WPI IRCN, Inst Adv Study UTIAS, Tokyo, Japan

来源：

KIDNEY INTERNATIONAL | 2019年 / 96卷 / 01期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

chronic kidney disease; ischemia-reperfusion injury; light-sheet fluorescent microscopy; sympathetic nerve; tissue clearing; SINGLE-CELL RESOLUTION; WHOLE-BODY; BRAIN;

D O I：

10.1016/j.kint.2019.02.011

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

The sympathetic nervous system is critical in maintaining the homeostasis of renal functions. However, its three-dimensional (3D) structures in the kidney have not been elucidated due to limitation of conventional imaging methods. CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) is a newly developed tissue-clearing technique, which enables whole-organ 3D imaging without thin-sectioning. Comprehensive 3D imaging by CUBIC found that sympathetic nerves are primarily distributed around arteries in the mouse kidney. Notably, the sympathetic innervation density was significantly decreased 10 days after ischemia-reperfusion injury (voluminal ratio of innervation area to kidney) by about 70%. Moreover, norepinephrine levels in kidney tissue (output of sympathetic nerves) were significantly reduced in injured kidneys by 77%, confirming sympathetic denervation after ischemia-reperfusion injury. Time-course imaging indicated that innervation partially recovered although overall denervation persisted 28 days after injury, indicating a continuous sympathetic nervous abnormality during the progression of chronic kidney disease. Thus, CUBIC-kidney, the 3D imaging analysis, can be a strong imaging tool, providing comprehensive, macroscopic perspectives for kidney research.

引用

页码：129 / 138

页数：10

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