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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)201-211
Number of pages11
JournalBrain Research
Volume1718
DOIs
Publication statusPublished - Sep 1 2019

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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

Cite this

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.

In: Brain Research, Vol. 1718, 01.09.2019, p. 201-211.

Research output: Contribution to journalArticle

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. In: Brain Research. 2019 ; Vol. 1718. pp. 201-211.
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