Mouse model of microembolic stroke and reperfusion

D. N. Atochin, J. C. Murciano, Y. Gürsoy-Özdemir, T. Krasik, F. Noda, C. Ayata, A. K. Dunn, M. A. Moskowitz, Paul L. Huang, V. R. Muzykantov

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background and Purpose-To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-μm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis. Methods-We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke. Results-Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain. Conclusions-We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA-/- mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.

Original languageEnglish
Pages (from-to)2177-2182
Number of pages6
JournalStroke
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 2004
Externally publishedYes

Fingerprint

Tissue Plasminogen Activator
Cerebrovascular Circulation
Reperfusion
Stroke
Fibrinolysis
Brain Infarction
Intracranial Embolism
Gene Knockout Techniques
Wounds and Injuries
Internal Carotid Artery
Fibrin
Knockout Mice
Brain Injuries
Thrombosis

Keywords

  • Animal models
  • Fibrinolysis
  • Microemboli
  • Stroke
  • Stroke, embolic

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Atochin, D. N., Murciano, J. C., Gürsoy-Özdemir, Y., Krasik, T., Noda, F., Ayata, C., ... Muzykantov, V. R. (2004). Mouse model of microembolic stroke and reperfusion. Stroke, 35(9), 2177-2182. https://doi.org/10.1161/01.STR.0000137412.35700.0e

Mouse model of microembolic stroke and reperfusion. / Atochin, D. N.; Murciano, J. C.; Gürsoy-Özdemir, Y.; Krasik, T.; Noda, F.; Ayata, C.; Dunn, A. K.; Moskowitz, M. A.; Huang, Paul L.; Muzykantov, V. R.

In: Stroke, Vol. 35, No. 9, 09.2004, p. 2177-2182.

Research output: Contribution to journalArticle

Atochin, DN, Murciano, JC, Gürsoy-Özdemir, Y, Krasik, T, Noda, F, Ayata, C, Dunn, AK, Moskowitz, MA, Huang, PL & Muzykantov, VR 2004, 'Mouse model of microembolic stroke and reperfusion', Stroke, vol. 35, no. 9, pp. 2177-2182. https://doi.org/10.1161/01.STR.0000137412.35700.0e
Atochin DN, Murciano JC, Gürsoy-Özdemir Y, Krasik T, Noda F, Ayata C et al. Mouse model of microembolic stroke and reperfusion. Stroke. 2004 Sep;35(9):2177-2182. https://doi.org/10.1161/01.STR.0000137412.35700.0e
Atochin, D. N. ; Murciano, J. C. ; Gürsoy-Özdemir, Y. ; Krasik, T. ; Noda, F. ; Ayata, C. ; Dunn, A. K. ; Moskowitz, M. A. ; Huang, Paul L. ; Muzykantov, V. R. / Mouse model of microembolic stroke and reperfusion. In: Stroke. 2004 ; Vol. 35, No. 9. pp. 2177-2182.
@article{0bee1cd36787448b8ab7dc5574eecdda,
title = "Mouse model of microembolic stroke and reperfusion",
abstract = "Background and Purpose-To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-μm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis. Methods-We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke. Results-Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain. Conclusions-We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA-/- mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.",
keywords = "Animal models, Fibrinolysis, Microemboli, Stroke, Stroke, embolic",
author = "Atochin, {D. N.} and Murciano, {J. C.} and Y. G{\"u}rsoy-{\"O}zdemir and T. Krasik and F. Noda and C. Ayata and Dunn, {A. K.} and Moskowitz, {M. A.} and Huang, {Paul L.} and Muzykantov, {V. R.}",
year = "2004",
month = "9",
doi = "10.1161/01.STR.0000137412.35700.0e",
language = "English",
volume = "35",
pages = "2177--2182",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Mouse model of microembolic stroke and reperfusion

AU - Atochin, D. N.

AU - Murciano, J. C.

AU - Gürsoy-Özdemir, Y.

AU - Krasik, T.

AU - Noda, F.

AU - Ayata, C.

AU - Dunn, A. K.

AU - Moskowitz, M. A.

AU - Huang, Paul L.

AU - Muzykantov, V. R.

PY - 2004/9

Y1 - 2004/9

N2 - Background and Purpose-To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-μm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis. Methods-We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke. Results-Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain. Conclusions-We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA-/- mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.

AB - Background and Purpose-To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-μm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis. Methods-We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke. Results-Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain. Conclusions-We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA-/- mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.

KW - Animal models

KW - Fibrinolysis

KW - Microemboli

KW - Stroke

KW - Stroke, embolic

UR - http://www.scopus.com/inward/record.url?scp=4344581565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344581565&partnerID=8YFLogxK

U2 - 10.1161/01.STR.0000137412.35700.0e

DO - 10.1161/01.STR.0000137412.35700.0e

M3 - Article

C2 - 15256680

AN - SCOPUS:4344581565

VL - 35

SP - 2177

EP - 2182

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 9

ER -