A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber

Teppei Komatsu, Hiroki Ohta, Naoki Takakura, Junichi Hata, Tomomichi Kitagawa, Yuta Kurashina, Hiroaki Onoe, Hirotaka James Okano, Yasuyuki Iguchi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The failure of neuroprotective treatment-related clinical trials, including stem cell therapies, may be partially due to a lack of suitable animal models. We have developed a stem cell-implantable radiopaque hydrogel microfiber that can survive for a long time in vivo. The microfiber is made of barium alginate hydrogel containing zirconium dioxide, fabricated in a dual coaxial laminar flow microfluidic device. We aimed to develop a novel focal stroke model using this microfiber. Using male Sprague-Dawley rats (n=14), a catheter (inner diameter, 0.42 mm; outer diameter, 0.55 mm) was navigated from the caudal ventral artery to the left internal carotid artery using digital subtraction angiography. A radiopaque hydrogel microfiber (diameter, 0.4 mm; length, 1 mm) was advanced through the catheter by slow injection of heparinized physiological saline to establish local occlusion. Both 9.4-T magnetic resonance imaging at 3 and 6 h and 2% 2,3,5-triphenyl tetrazolium chloride staining at 24 h after stroke model creation were performed. Neurological deficit score and body temperature were measured. The anterior cerebral artery-middle cerebral artery bifurcation was selectively embolized in all rats. Median operating time was 4 min (interquartile range [IQR], 3–8 min). Mean infarct volume was 388 mm3 (IQR, 354–420 mm3) at 24 h after occlusion. No infarction of the thalamus or hypothalamus was seen. Body temperature did not change significantly over time (P = 0.204). However, neurological deficit scores before and at 3, 6, and 24 h after model creation differed significantly (P < 0.001). We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of "pure" cell transplantation in treating stroke.

Original languageEnglish
JournalTranslational Stroke Research
DOIs
Publication statusAccepted/In press - 2023

Keywords

  • Animal model
  • Ischemic stroke
  • Middle cerebral artery occlusion
  • Rat
  • Regeneration
  • Stem cell

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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