Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats

Gono, Rina; Sugimoto, Kana; Yang, Chihpin; Murata, Yukie; Nomura, Reiko; Shirazaki, Mai; Harada, Kazuo; Harada, Teiji; Miyashita, Yohei; Higashisaka, Kazuma; Katada, Ryuichi; Matsumoto, Hiroshi

doi:https://doi.org/10.1177/0271678X231151569

Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats

Gono, Rina; Sugimoto, Kana; Yang, Chihpin et al.

Journal of Cerebral Blood Flow and Metabolism, 2023, 43(5), 812-827

Number of Access:1,534（2025-07-20 21:42 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/92440

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Title	Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats
Creator	CreatorName Gono, Rina
	NRID 1000000581034 1000000581034 ORCID 0000-0002-6850-3005 0000-0002-6850-3005 researchmap permalink kana_sugimoto kana_sugimoto Scopus Author ID 26039543700 26039543700 CreatorName Sugimoto, Kana
	NRID 1000010852543 1000010852543 researchmap permalink cpyang cpyang CreatorName Yang, Chihpin
	CreatorName Murata, Yukie
	CreatorName Nomura, Reiko
	CreatorName Shirazaki, Mai
	NRID 1000050397741 1000050397741 ORCID 0000-0002-9348-1629 0000-0002-9348-1629 researchmap permalink read0204933 read0204933 Scopus Author ID 16549528100 16549528100 CreatorName Harada, Kazuo
	CreatorName Harada, Teiji
	NRID 1000060816312 1000060816312 ORCID 0000-0002-1739-4734 0000-0002-1739-4734 researchmap permalink y-miyashita y-miyashita Scopus Author ID 57208672131 57208672131 CreatorName Miyashita, Yohei
	NRID 1000020646757 1000020646757 researchmap permalink read646757 read646757 Scopus Author ID 35603386200 35603386200 CreatorName Higashisaka, Kazuma
	NRID 1000000423757 1000000423757 researchmap permalink yuukisaya yuukisaya Scopus Author ID 24168659200 24168659200 CreatorName Katada, Ryuichi
	NRID 1000060263092 1000060263092 ORCID 0000-0001-9560-0030 0000-0001-9560-0030 researchmap permalink read0183835 read0183835 Scopus Author ID 55245010500 55245010500 CreatorName Matsumoto, Hiroshi
Subject	Aquaporin-4
	brain edema
	exercise
	IL-1RA
	myokine
Description	Gono R., Sugimoto K., Yang C., et al. Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats. Journal of Cerebral Blood Flow and Metabolism, 43(5), 812-827. © 2023 SAGE Publishing. DOI: 10.1177/0271678X231151569.
Abstract	Cerebral edema following cerebral infarction can be severe and directly affect mortality and mobility. Exercise therapy after cerebral infarction is an effective therapeutic approach; however, the molecular mechanism remains unclear. Myokines such as interleukin-1 receptor antagonist (IL-1RA) are released during skeletal muscle contraction with effects on other organs. We hypothesized that myokine release during exercise might improve brain edema and confirmed the hypothesis using transient middle cerebral artery occlusion (tMCAO) model rats. Rats subjected to tMCAO were divided according to the severity of illness and further assigned to exercise and non-exercise groups. Treadmill exercises were performed at a speed of 2–8 m/min for 10 min from 1–6 days post-reperfusion after tMCAO. Exercise significantly reduced edema and neurological deficits in severely ill rats, with a reduction in aquaporin-4 (AQP4) expression in the ischemic core and increased blood IL-1RA release from the stroke-unaffected hindlimb muscle after tMCAO. Administration of IL-1RA into the lateral ventricles significantly reduced edema and AQP4 expression in the ischemic core. In conclusion, treadmill exercise performed in the early phase of stroke onset alleviated the decrease in blood IL-1RA following ischemic stroke. IL-1RA administration decreased astrocytic AQP4 expression in the ischemic core, suppressing brain edema.
Publisher	SAGE Publications Ltd
Source Title	Journal of Cerebral Blood Flow and Metabolism
Volume (Issue)	43(5)
Page	812-827
Date of Issued	2023-05-01
Language	English
Handle URL	https://hdl.handle.net/11094/92440
PISSN	0271678X
eISSN	15597016
NCID	AA10458430
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1177/0271678X231151569
Access Rights	open access
CopyRight	Copyright © 2023 SAGE Publishing
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Cerebral Blood Flow and Metabolism. 2023, 43(5), p. 812-827
DC.title	Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats
DC.creator	Gono, Rina
	Sugimoto, Kana
	Yang, Chihpin
	Murata, Yukie
	Nomura, Reiko
	Shirazaki, Mai
	Harada, Kazuo
	Harada, Teiji
	Miyashita, Yohei
	Higashisaka, Kazuma
	Katada, Ryuichi
	Matsumoto, Hiroshi
DC.publisher	SAGE Publications Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-05-01
DC.identifier	https://doi.org/10.1177/0271678X231151569
DC.subject	Aquaporin-4
	brain edema
	exercise
	IL-1RA
	myokine
DC.description	Gono R., Sugimoto K., Yang C., et al. Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats. Journal of Cerebral Blood Flow and Metabolism, 43(5), 812-827. © 2023 SAGE Publishing. DOI: 10.1177/0271678X231151569.
DCTERMS.abstract	Cerebral edema following cerebral infarction can be severe and directly affect mortality and mobility. Exercise therapy after cerebral infarction is an effective therapeutic approach; however, the molecular mechanism remains unclear. Myokines such as interleukin-1 receptor antagonist (IL-1RA) are released during skeletal muscle contraction with effects on other organs. We hypothesized that myokine release during exercise might improve brain edema and confirmed the hypothesis using transient middle cerebral artery occlusion (tMCAO) model rats. Rats subjected to tMCAO were divided according to the severity of illness and further assigned to exercise and non-exercise groups. Treadmill exercises were performed at a speed of 2–8 m/min for 10 min from 1–6 days post-reperfusion after tMCAO. Exercise significantly reduced edema and neurological deficits in severely ill rats, with a reduction in aquaporin-4 (AQP4) expression in the ischemic core and increased blood IL-1RA release from the stroke-unaffected hindlimb muscle after tMCAO. Administration of IL-1RA into the lateral ventricles significantly reduced edema and AQP4 expression in the ischemic core. In conclusion, treadmill exercise performed in the early phase of stroke onset alleviated the decrease in blood IL-1RA following ischemic stroke. IL-1RA administration decreased astrocytic AQP4 expression in the ischemic core, suppressing brain edema.
DC.rights	Copyright © 2023 SAGE Publishing
DC.format	92440
citation_title	Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats
citation_author	Gono, Rina
	Sugimoto, Kana
	Yang, Chihpin
	Murata, Yukie
	Nomura, Reiko
	Shirazaki, Mai
	Harada, Kazuo
	Harada, Teiji
	Miyashita, Yohei
	Higashisaka, Kazuma
	Katada, Ryuichi
	Matsumoto, Hiroshi
citation_publisher	SAGE Publications Ltd
citation_language	English
citation_date	2023-05-01
citation_journal_title	Journal of Cerebral Blood Flow and Metabolism
citation_volume	43
citation_issue	5
citation_firstpage	812
citation_lastpage	827
citation_doi	https://doi.org/10.1177/0271678X231151569
citation_public_url	https://hdl.handle.net/11094/92440

Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats

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