A novel mouse model of thromboembolic stroke

Yingxin Chen, Wenbin Zhu, Wenri Zhang, Nicole Libal, Stephanie J. Murphy, Halina Offner, Nabil Alkayed

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. Results: The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15 min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24 h after thrombosis in both WT and DR2-Tg. Comparison with Existing Methods: Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. Conclusion: We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalJournal of Neuroscience Methods
Volume256
DOIs
StatePublished - Dec 30 2015

Fingerprint

Tissue Plasminogen Activator
Stroke
Lasers
Thrombosis
Catheters
Perfusion
Thrombin
Cerebral Arteries
Middle Cerebral Artery Infarction
Internal Carotid Artery
HLA Antigens
Infarction
Transgenic Mice
Anesthesia
Air
Injections
Mortality

Keywords

  • Cerebral ischemia
  • Mouse
  • Optical microangiography
  • Stroke
  • Thromboembolic
  • tPA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A novel mouse model of thromboembolic stroke. / Chen, Yingxin; Zhu, Wenbin; Zhang, Wenri; Libal, Nicole; Murphy, Stephanie J.; Offner, Halina; Alkayed, Nabil.

In: Journal of Neuroscience Methods, Vol. 256, 30.12.2015, p. 203-211.

Research output: Contribution to journalArticle

Chen, Yingxin ; Zhu, Wenbin ; Zhang, Wenri ; Libal, Nicole ; Murphy, Stephanie J. ; Offner, Halina ; Alkayed, Nabil. / A novel mouse model of thromboembolic stroke. In: Journal of Neuroscience Methods. 2015 ; Vol. 256. pp. 203-211.
@article{69f027fc31614b64af40cdeb338ac612,
title = "A novel mouse model of thromboembolic stroke",
abstract = "Background: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. Results: The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15 min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24 h after thrombosis in both WT and DR2-Tg. Comparison with Existing Methods: Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. Conclusion: We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.",
keywords = "Cerebral ischemia, Mouse, Optical microangiography, Stroke, Thromboembolic, tPA",
author = "Yingxin Chen and Wenbin Zhu and Wenri Zhang and Nicole Libal and Murphy, {Stephanie J.} and Halina Offner and Nabil Alkayed",
year = "2015",
month = "12",
day = "30",
doi = "10.1016/j.jneumeth.2015.09.013",
language = "English (US)",
volume = "256",
pages = "203--211",
journal = "Journal of Neuroscience Methods",
issn = "0165-0270",
publisher = "Elsevier",

}

TY - JOUR

T1 - A novel mouse model of thromboembolic stroke

AU - Chen, Yingxin

AU - Zhu, Wenbin

AU - Zhang, Wenri

AU - Libal, Nicole

AU - Murphy, Stephanie J.

AU - Offner, Halina

AU - Alkayed, Nabil

PY - 2015/12/30

Y1 - 2015/12/30

N2 - Background: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. Results: The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15 min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24 h after thrombosis in both WT and DR2-Tg. Comparison with Existing Methods: Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. Conclusion: We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.

AB - Background: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. Results: The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15 min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24 h after thrombosis in both WT and DR2-Tg. Comparison with Existing Methods: Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. Conclusion: We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.

KW - Cerebral ischemia

KW - Mouse

KW - Optical microangiography

KW - Stroke

KW - Thromboembolic

KW - tPA

UR - http://www.scopus.com/inward/record.url?scp=84942525869&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942525869&partnerID=8YFLogxK

U2 - 10.1016/j.jneumeth.2015.09.013

DO - 10.1016/j.jneumeth.2015.09.013

M3 - Article

C2 - 26386284

AN - SCOPUS:84942525869

VL - 256

SP - 203

EP - 211

JO - Journal of Neuroscience Methods

JF - Journal of Neuroscience Methods

SN - 0165-0270

ER -