TY - JOUR
T1 - Embolic middle cerebral artery occlusion model using thrombin and fibrinogen composed clots in rat
AU - Ren, Ming
AU - Lin, Zi Jing
AU - Qian, Hai
AU - Choudhury, Gourav Roy
AU - Liu, Ran
AU - Liu, Hanli
AU - Yang, Shao Hua
N1 - Funding Information:
This project was supported in part by NIH grants R01NS054687 (SY), R01NS054651 (SY), R21/R33NS052850 (HL).
PY - 2012/11/15
Y1 - 2012/11/15
N2 - 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 1. h 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.
AB - 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 1. h 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.
KW - Embolism
KW - Ischemia
KW - Middle cerebral artery
KW - Recombinant tissue plasminogen activator
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84867588598&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2012.09.006
DO - 10.1016/j.jneumeth.2012.09.006
M3 - Article
C2 - 22985597
AN - SCOPUS:84867588598
SN - 0165-0270
VL - 211
SP - 296
EP - 304
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 2
ER -