A novel atherothrombotic model of ischemic stroke induced by injection of collagen into the cerebral vasculature

作者：Schunke Kathryn J; Toung Thomas K; Zhang Jian; Pathak Arvind P; Xu Jiadi; Zhang Jiangyang; Koehler Raymond C; Faraday Nauder^*

来源：Journal of Neuroscience Methods, 2015, 239: 65-74.

DOI：10.1016/j.jneumeth.2014.10.001

• Atherothrombosis
• Collagen
• Ischemic stroke
• Platelet
• Mouse
• Rat

Background: Most ischemic strokes in humans are caused by ruptured arterial atheroma, which activate platelets and produce thrombi that occlude cerebral vessels.
Methods: To simulate these events, we threaded a catheter through the internal carotid artery toward the middle cerebral artery (MCA) orifice and injected collagen directly into the cerebral circulation of male C57Bl/6 mice and Wistar rats.
Results: Laser-Doppler flowmetry demonstrated reductions in cerebral blood flow (CBF) of similar to 80% in mice and similar to 60% in rats. CBF spontaneously increased but remained depressed after catheter withdrawal. Magnetic resonance imaging showed that ipsilateral CBF was reduced at 3 h after collagen injection and markedly improved at 48 h. Micro-computed tomography revealed reduced blood vessel density in the ipsilateral MCA territory at 3 h. Gross examination of excised brains revealed thrombi within ipsilateral cerebral arteries at 3 h, but not 24 h, after collagen injection. Immunofluorescence microscopy confirmed that platelets and fibrinogen/fibrin were major components of these thrombi at both macrovascular and microvascular levels. Cerebral infarcts comprising similar to 30% of hemispheric volume and neurobehavioral deficits were observed 48 h after ischemic injury in both mice and rats.
Comparison with existing methods: Collagen injection caused brain injury that was similar in magnitude and variability to mechanical MCA occlusion or injection of a pre-formed clot; however, alterations in CBF and the mechanism of vascular occlusion were more consistent with clinical ischemic stroke.
Conclusion: This novel rodent model of ischemic stroke has pathophysiologic characteristics consistent with clinical atherothrombotic stroke, is technically feasible, and creates reproducible brain injury.

• 出版日期2015-1-15