Potential circadian effects on translational failure for neuroprotection

doi:10.1038/s41586-020-2348-z

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2348-z
	Potential circadian effects on translational failure for neuroprotection
	Sakai, Akito 1,2,3; Minami, Susumu 4,5; Koretsune, Takashi 1,6; Chen, Taishi 1,3; Higo, Tomoya 1,3; Wang, Yangming 1; Nomoto, Takuya 7; Hirayama, Motoaki 5; Miwa, Shinji 1,3,8; Nishio-Hamane, Daisuke 1; Ishii, Fumiyuki 4,5; Arita, Ryotaro 3,5,7; Nakatsuji, Satoru 1,2,3,8,9,10
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
文章类型	Article;Early Access
语种	英语
国家	USA; South Korea; Peoples R China
英文关键词	Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans(1,2) may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger alpha-phenyl-butyl-tert-nitrone (alpha PBN), and the N-methyl-d-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in ' active-phase' than in ' inactive-phase' rodent neurons. alpha PBN and MK801 reduced neuronal death only in ' inactive-phase' neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases. Studies in rats and mice at different times of day suggest that the failure of neuroprotective strategies for stroke in translational studies might be related to the difference in circadian cycles between humans and rodents.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000537932200008
WOS关键词	CEREBRAL-ISCHEMIA ; ACUTE STROKE ; CELL-DEATH ; NXY-059 ; MK-801 ; DAMAGE ; CLOCK ; RATS ; OPPORTUNITIES ; THRESHOLDS
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计	被引频次：134[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281335
专题	地球科学资源环境科学气候变化
作者单位	1.Univ Tokyo, Inst Solid State Phys, Kashiwa, Chiba, Japan; 2.Univ Tokyo, Dept Phys, Tokyo, Japan; 3.Japan Sci & Technol Agcy JST, CREST, Honcho, Kawaguchi, Saitama, Japan; 4.Kanazawa Univ, Nanomat Res Inst, Kanazawa, Ishikawa, Japan; 5.RIKEN, Ctr Emergent Matter Sci CEMS, Wako, Saitama, Japan; 6.Tohoku Univ, Dept Phys, Sendai, Miyagi, Japan; 7.Univ Tokyo, Dept Appl Phys, Tokyo, Japan; 8.Univ Tokyo, Trans Scale Quantum Sci Inst, Tokyo, Japan; 9.Johns Hopkins Univ, Inst Quantum Matter, Baltimore, MD 21218 USA; 10.Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA
推荐引用方式 GB/T 7714	Sakai, Akito,Minami, Susumu,Koretsune, Takashi,et al. Potential circadian effects on translational failure for neuroprotection[J]. NATURE,2020.
APA	Sakai, Akito.,Minami, Susumu.,Koretsune, Takashi.,Chen, Taishi.,Higo, Tomoya.,...&Nakatsuji, Satoru.(2020).Potential circadian effects on translational failure for neuroprotection.NATURE.
MLA	Sakai, Akito,et al."Potential circadian effects on translational failure for neuroprotection".NATURE (2020).