Early initiation of a factor Xa inhibitor can attenuate tissue repair and neurorestoration after middle cerebral artery occlusion

Motohiro Komori, Tetsuro Ago, Yoshinobu Wakisaka, Kuniyuki Nakamura, Masaki Tachibana, Yoji Yoshikawa, Tomoya Shibahara, Kei Yamanaka, Junya Kuroda, Takanari Kitazono

研究成果: ジャーナルへの寄稿記事

抄録

The timing of anti-coagulation therapy initiation after acute cardioembolic stroke remains controversial. We investigated the effects of post-stroke administration of a factor Xa inhibitor in mice, focusing on tissue repair and functional restoration outcomes. We initiated administration of rivaroxaban, a Xa inhibitor, immediately after permanent distal middle cerebral artery occlusion (pMCAO)in CB-17 mice harboring few leptomeningeal anastomoses at baseline. Rivaroxaban initiated immediately after pMCAO hindered the recovery of blood flow in ischemic areas by inhibiting leptomeningeal anastomosis development, and led to impaired restoration of neurologic functions with less extensive peri-infarct astrogliosis. Within infarct areas, angiogenesis and fibrotic responses were attenuated in rivaroxaban-fed mice. Furthermore, inflammatory responses, including the accumulation of neutrophils and monocytes/macrophages, local secretion of pro-inflammatory cytokines, and breakdown of the blood–brain barrier, were enhanced in infarct areas in mice treated immediately with rivaroxaban following pMCAO. The detrimental effects were not found when rivaroxaban was initiated after transient MCAO or on day 7 after pMCAO. Collectively, early post-stroke initiation of a factor Xa inhibitor may suppress leptomeningeal anastomosis development and blood flow recovery in ischemic areas, thereby resulting in attenuated tissue repair and functional restoration unless occluded large arteries are successfully recanalized.

元の言語英語
ページ(範囲)201-211
ページ数11
ジャーナルBrain Research
1718
DOI
出版物ステータス出版済み - 9 1 2019

Fingerprint

Peptide Initiation Factors
Middle Cerebral Artery Infarction
Stroke
Nervous System
Monocytes
Neutrophils
Arteries
Macrophages
Rivaroxaban
Factor Xa Inhibitors
Cytokines

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

これを引用

Early initiation of a factor Xa inhibitor can attenuate tissue repair and neurorestoration after middle cerebral artery occlusion. / Komori, Motohiro; Ago, Tetsuro; Wakisaka, Yoshinobu; Nakamura, Kuniyuki; Tachibana, Masaki; Yoshikawa, Yoji; Shibahara, Tomoya; Yamanaka, Kei; Kuroda, Junya; Kitazono, Takanari.

:: Brain Research, 巻 1718, 01.09.2019, p. 201-211.

研究成果: ジャーナルへの寄稿記事

Komori, Motohiro ; Ago, Tetsuro ; Wakisaka, Yoshinobu ; Nakamura, Kuniyuki ; Tachibana, Masaki ; Yoshikawa, Yoji ; Shibahara, Tomoya ; Yamanaka, Kei ; Kuroda, Junya ; Kitazono, Takanari. / Early initiation of a factor Xa inhibitor can attenuate tissue repair and neurorestoration after middle cerebral artery occlusion. :: Brain Research. 2019 ; 巻 1718. pp. 201-211.
@article{97065f538b1e45f0b966dcd8e7e37482,
title = "Early initiation of a factor Xa inhibitor can attenuate tissue repair and neurorestoration after middle cerebral artery occlusion",
abstract = "The timing of anti-coagulation therapy initiation after acute cardioembolic stroke remains controversial. We investigated the effects of post-stroke administration of a factor Xa inhibitor in mice, focusing on tissue repair and functional restoration outcomes. We initiated administration of rivaroxaban, a Xa inhibitor, immediately after permanent distal middle cerebral artery occlusion (pMCAO)in CB-17 mice harboring few leptomeningeal anastomoses at baseline. Rivaroxaban initiated immediately after pMCAO hindered the recovery of blood flow in ischemic areas by inhibiting leptomeningeal anastomosis development, and led to impaired restoration of neurologic functions with less extensive peri-infarct astrogliosis. Within infarct areas, angiogenesis and fibrotic responses were attenuated in rivaroxaban-fed mice. Furthermore, inflammatory responses, including the accumulation of neutrophils and monocytes/macrophages, local secretion of pro-inflammatory cytokines, and breakdown of the blood–brain barrier, were enhanced in infarct areas in mice treated immediately with rivaroxaban following pMCAO. The detrimental effects were not found when rivaroxaban was initiated after transient MCAO or on day 7 after pMCAO. Collectively, early post-stroke initiation of a factor Xa inhibitor may suppress leptomeningeal anastomosis development and blood flow recovery in ischemic areas, thereby resulting in attenuated tissue repair and functional restoration unless occluded large arteries are successfully recanalized.",
author = "Motohiro Komori and Tetsuro Ago and Yoshinobu Wakisaka and Kuniyuki Nakamura and Masaki Tachibana and Yoji Yoshikawa and Tomoya Shibahara and Kei Yamanaka and Junya Kuroda and Takanari Kitazono",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.brainres.2019.05.020",
language = "English",
volume = "1718",
pages = "201--211",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Early initiation of a factor Xa inhibitor can attenuate tissue repair and neurorestoration after middle cerebral artery occlusion

AU - Komori, Motohiro

AU - Ago, Tetsuro

AU - Wakisaka, Yoshinobu

AU - Nakamura, Kuniyuki

AU - Tachibana, Masaki

AU - Yoshikawa, Yoji

AU - Shibahara, Tomoya

AU - Yamanaka, Kei

AU - Kuroda, Junya

AU - Kitazono, Takanari

PY - 2019/9/1

Y1 - 2019/9/1

N2 - The timing of anti-coagulation therapy initiation after acute cardioembolic stroke remains controversial. We investigated the effects of post-stroke administration of a factor Xa inhibitor in mice, focusing on tissue repair and functional restoration outcomes. We initiated administration of rivaroxaban, a Xa inhibitor, immediately after permanent distal middle cerebral artery occlusion (pMCAO)in CB-17 mice harboring few leptomeningeal anastomoses at baseline. Rivaroxaban initiated immediately after pMCAO hindered the recovery of blood flow in ischemic areas by inhibiting leptomeningeal anastomosis development, and led to impaired restoration of neurologic functions with less extensive peri-infarct astrogliosis. Within infarct areas, angiogenesis and fibrotic responses were attenuated in rivaroxaban-fed mice. Furthermore, inflammatory responses, including the accumulation of neutrophils and monocytes/macrophages, local secretion of pro-inflammatory cytokines, and breakdown of the blood–brain barrier, were enhanced in infarct areas in mice treated immediately with rivaroxaban following pMCAO. The detrimental effects were not found when rivaroxaban was initiated after transient MCAO or on day 7 after pMCAO. Collectively, early post-stroke initiation of a factor Xa inhibitor may suppress leptomeningeal anastomosis development and blood flow recovery in ischemic areas, thereby resulting in attenuated tissue repair and functional restoration unless occluded large arteries are successfully recanalized.

AB - The timing of anti-coagulation therapy initiation after acute cardioembolic stroke remains controversial. We investigated the effects of post-stroke administration of a factor Xa inhibitor in mice, focusing on tissue repair and functional restoration outcomes. We initiated administration of rivaroxaban, a Xa inhibitor, immediately after permanent distal middle cerebral artery occlusion (pMCAO)in CB-17 mice harboring few leptomeningeal anastomoses at baseline. Rivaroxaban initiated immediately after pMCAO hindered the recovery of blood flow in ischemic areas by inhibiting leptomeningeal anastomosis development, and led to impaired restoration of neurologic functions with less extensive peri-infarct astrogliosis. Within infarct areas, angiogenesis and fibrotic responses were attenuated in rivaroxaban-fed mice. Furthermore, inflammatory responses, including the accumulation of neutrophils and monocytes/macrophages, local secretion of pro-inflammatory cytokines, and breakdown of the blood–brain barrier, were enhanced in infarct areas in mice treated immediately with rivaroxaban following pMCAO. The detrimental effects were not found when rivaroxaban was initiated after transient MCAO or on day 7 after pMCAO. Collectively, early post-stroke initiation of a factor Xa inhibitor may suppress leptomeningeal anastomosis development and blood flow recovery in ischemic areas, thereby resulting in attenuated tissue repair and functional restoration unless occluded large arteries are successfully recanalized.

UR - http://www.scopus.com/inward/record.url?scp=85065848289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065848289&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2019.05.020

DO - 10.1016/j.brainres.2019.05.020

M3 - Article

VL - 1718

SP - 201

EP - 211

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -