title: Embolic middle cerebral artery occlusion model using thrombin and fibrinogen composed clots in rat.
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.
authors.affiliation: Department of Pharmacology & Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ren
authors.forename: Zi-Jing
authors.initials: ZJ
authors.lastname: Lin
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Gourav Roy
authors.initials: GR
authors.lastname: Choudhury
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Hanli
authors.initials: H
authors.lastname: Liu
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D004195:Disease Models, Animal; D005340:Fibrinogen; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin; D013927:Thrombosis; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D005340:Fibrinogen; D013917:Thrombin; D010959:Tissue Plasminogen Activator