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Title: Transient receptor potential canonical 3 inhibitor Pyr3 improves outcomes and attenuates astrogliosis after intracerebral hemorrhage in mice.
Authors: Munakata, Masaya
Shirakawa, Hisashi  kyouindb  KAKEN_id
Nagayasu, Kazuki  kyouindb  KAKEN_id
Miyanohara, Jun
Miyake, Takahito  kyouindb  KAKEN_id
Nakagawa, Takayuki  kyouindb  KAKEN_id
Katsuki, Hiroshi
Kaneko, Shuji  kyouindb  KAKEN_id
Author's alias: 白川, 久志
金子, 周司
Issue Date: Jul-2013
Publisher: American Heart Association
Journal title: Stroke
Volume: 44
Issue: 7
Start page: 1981
End page: 1987
Abstract: Background and Purpose—Intracerebral hemorrhage (ICH) stems from the rupture of blood vessels in the brain, with the subsequent accumulation of blood in the parenchyma. Increasing evidence suggests that blood-derived factors induce excessive inflammatory responses that are involved in the progression of ICH-induced brain injury. Thrombin, a major blood-derived factor, leaks into the brain parenchyma on blood–brain barrier disruption and induces brain injury and astrogliosis. Furthermore, thrombin dynamically upregulates transient receptor potential canonical 3 channel, which contributes to pathological astrogliosis through a feed-forward upregulation of its own expression. The present study investigated whether Ethyl-1-(4-(2, 3, 3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), a specific transient receptor potential canonical 3 inhibitor, can improve functional outcomes and attenuate astrogliosis after ICH in mice. Methods—Male C57BL6 mice received an intracerebral infusion of collagenase or autologous blood to induce ICH. Pyr3 was given both intracerebroventricularly and intraperitoneally after ICH induction. ICH-induced brain injury was evaluated by quantitative assessment of neurological deficits, brain swelling, and injury volume after ICH. Astrocyte activation was evaluated by immunohistochemical assessment of changes in S100 protein expression. Results—Neurological deficits, neuronal injury, brain edema, and astrocyte activation were all significantly improved by administration of Pyr3. Moreover, delayed administration of Pyr3 at 6 hours or 1 day after blood or collagenase infusion, respectively, also improved the symptoms. Conclusions—Pyr3, a specific inhibitor of transient receptor potential canonical 3, reduced the perihematomal accumulation of astrocytes and ameliorated ICH–induced brain injury. Therefore, transient receptor potential canonical 3 provides a new therapeutic target for the treatment of hemorrhagic brain injury.
Rights: © 2013 American Heart Association, Inc.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/187123
DOI(Published Version): 10.1161/STROKEAHA.113.679332
PubMed ID: 23674527
Appears in Collections:Journal Articles

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