Embolic Middle Cerebral Artery Occlusion Model Using Thrombin and Fibrinogen Composed Clots in Rat

Overview

Journal J Neurosci Methods

Specialty Neurology

Date 2012 Sep 19

PMID 22985597

Citations 17

Authors

Ming Ren

Zi-Jing Lin

Hai Qian

Gourav Roy Choudhury

Ran Liu

Hanli Liu

Shao-Hua Yang

Affiliations

Soon will be listed here.

Abstract

Ischemic stroke accounts for over 80% in total human stroke which mostly affect middle cerebral artery (MCA) territory. Embolic stroke models induced by injection of homologous clots into the internal carotid artery and MCA closely mimic human stroke and have been commonly used in stroke research. Studies indicate that the size and composition of clots are critical for the reproducibility of the stroke model. In the present study, we modified the homologous clots formation by addition of thrombin and fibrinogen which produced even distribution of fibrin with tight cross linkage of red blood cells. We optimized the embolic MCA occlusion model in rats using different size of the mixed clots. A precise lodgment of the clots at the MCA bifurcation and highly reproducible ischemic lesion in the MCA territory were demonstrated in the embolic MCA occlusion model induced by injection of 10 pieces of 1-mm long mixed clots made in PE-60 catheter. We further tested the effect of recombinant tissue plasminogen activator (rtPA) in this embolic MCA occlusion model. rtPA induced thrombolysis, improved neurological outcome, and significantly reduced ischemic lesion volume when administered at 1h after embolism as compared with control. In summary, we have established a reproducible embolic MCA occlusion model using clots made of homologous blood, thrombin and fibrinogen. The mixed clots enable precise lodgment at the MCA bifurcation which is responsive to thrombolytic therapy of rtPA.

Citing Articles

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References

Hossmann K . Cerebral ischemia: models, methods and outcomes. Neuropharmacology. 2008; 55(3):257-70. DOI: 10.1016/j.neuropharm.2007.12.004. View

Zivin J . Thrombolytic stroke therapy: past, present, and future. Neurology. 1999; 53(1):14-9. DOI: 10.1212/wnl.53.1.14. View

BUSCH E, Kruger K, Hossmann K . Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat. Brain Res. 1998; 778(1):16-24. DOI: 10.1016/s0006-8993(97)01008-1. View

Mayzel-Oreg O, Omae T, Kazemi M, Li F, Fisher M, Cohen Y . Microsphere-induced embolic stroke: an MRI study. Magn Reson Med. 2004; 51(6):1232-8. DOI: 10.1002/mrm.20100. View

Overgaard K, Sereghy T, Boysen G, Pedersen H, Hoyer S, Diemer N . A rat model of reproducible cerebral infarction using thrombotic blood clot emboli. J Cereb Blood Flow Metab. 1992; 12(3):484-90. DOI: 10.1038/jcbfm.1992.66. View

Zhang R, Chopp M, Zhang Z, Jiang Q, Ewing J . A rat model of focal embolic cerebral ischemia. Brain Res. 1997; 766(1-2):83-92. DOI: 10.1016/s0006-8993(97)00580-5. View

Niu H, Tian F, Lin Z, Liu H . Development of a compensation algorithm for accurate depth localization in diffuse optical tomography. Opt Lett. 2010; 35(3):429-31. DOI: 10.1364/OL.35.000429. View

DiNapoli V, Rosen C, Nagamine T, Crocco T . Selective MCA occlusion: a precise embolic stroke model. J Neurosci Methods. 2006; 154(1-2):233-8. DOI: 10.1016/j.jneumeth.2005.12.026. View

Beech J, Williams S, Campbell C, Bath P, Parsons A, Hunter A . Further characterisation of a thromboembolic model of stroke in the rat. Brain Res. 2001; 895(1-2):18-24. DOI: 10.1016/s0006-8993(00)03331-x. View

10.

Wang X, Tsuji K, Lee S, Ning M, Furie K, Buchan A . Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke. Stroke. 2004; 35(11 Suppl 1):2726-30. DOI: 10.1161/01.STR.0000143219.16695.af. View

11.

Gillum R . New considerations in analyzing stroke and heart disease mortality trends: the Year 2000 Age Standard and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Stroke. 2002; 33(6):1717-21. DOI: 10.1161/01.str.0000016925.58848.ea. View

12.

Orset C, Macrez R, Young A, Panthou D, Angles-Cano E, Maubert E . Mouse model of in situ thromboembolic stroke and reperfusion. Stroke. 2007; 38(10):2771-8. DOI: 10.1161/STROKEAHA.107.487520. View

13.

Gerriets T, Li F, Silva M, Meng X, Brevard M, Sotak C . The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats. J Neurosci Methods. 2003; 122(2):201-11. DOI: 10.1016/s0165-0270(02)00322-9. View

14.

Kudo M, Aoyama A, Ichimori S, Fukunaga N . An animal model of cerebral infarction. Homologous blood clot emboli in rats. Stroke. 1982; 13(4):505-8. DOI: 10.1161/01.str.13.4.505. View

15.

Durukan A, Tatlisumak T . Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. Pharmacol Biochem Behav. 2007; 87(1):179-97. DOI: 10.1016/j.pbb.2007.04.015. View

16.

Carmichael S . Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx. 2006; 2(3):396-409. PMC: 1144484. DOI: 10.1602/neurorx.2.3.396. View

17.

Del Zoppo G . Antithrombotic treatments in acute ischemic stroke. Curr Opin Hematol. 2000; 7(5):309-15. DOI: 10.1097/00062752-200009000-00009. View

18.

Henninger N, Sicard K, Schmidt K, Bardutzky J, Fisher M . Comparison of ischemic lesion evolution in embolic versus mechanical middle cerebral artery occlusion in Sprague Dawley rats using diffusion and perfusion imaging. Stroke. 2006; 37(5):1283-7. DOI: 10.1161/01.STR.0000217223.72193.98. View

19.

Stehling F, Weber R, Ozcelik A, Brocker M, Volbracht L, Diener H . Acute changes of coagulation and fibrinolysis parameters after experimental thromboembolic stroke and thrombolytic therapy. Neurosci Lett. 2008; 441(1):39-43. DOI: 10.1016/j.neulet.2008.05.102. View

20.

Lindgren A, Lindoff C, Norrving B, ASTEDT B, Johansson B . Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients. Stroke. 1996; 27(6):1066-71. DOI: 10.1161/01.str.27.6.1066. View