Mouse model of microembolic stroke and reperfusion

• Published in: Stroke (1970) Vol. 35; no. 9; pp. 2177 - 2182
• Main Authors: ATOCHIN, D. N, MURCIANO, J. C, GÜRSOY-ÖZDEMIR, Y, KRASIK, T, NODA, F, AYATA, C, DUNN, A. K, MOSKOWITZ, M. A, HUANG, P. L, MUZYKANTOV, V. R
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-09-2004
• Subjects: Animals; Biological and medical sciences; Brain Damage, Chronic - etiology; Brain Ischemia - etiology; Carotid Artery, Internal; Cerebral Infarction - etiology; Disease Models, Animal; Fibrin - administration & dosage; Fibrinolysis; Injections, Intra-Arterial; Injections, Intravenous; Intracranial Embolism - complications; Intracranial Embolism - physiopathology; Iodine Radioisotopes - pharmacokinetics; Laser-Doppler Flowmetry; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurology; Particle Size; Reperfusion; Tail - blood supply; Tissue Distribution; Tissue Plasminogen Activator - deficiency; Tissue Plasminogen Activator - genetics; Tissue Plasminogen Activator - physiology; Vascular diseases and vascular malformations of the nervous system; Animal model; microemboli; Stroke; Nervous system diseases; animal models; Rodentia; Cardiovascular disease; Fibrinolysis; Cerebral disorder; Vascular disease; Vertebrata; stroke, embolic; Mammalia; Reperfusion; Mouse; Animal; Central nervous system disease; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.str.0000137412.35700.0e

To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-microm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis.
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.
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.
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.