Microemboli May Link Spreading Depression, Migraine Aura, and Patent Foramen Ovale

被引:259
作者
Nozari, Ala [1 ,2 ]
Dilekoz, Ergin [1 ]
Sukhotinsky, Inna [1 ]
Stein, Thor [3 ]
Eikermann-Haerter, Katharina [1 ]
Liu, Christina [4 ]
Wang, Yumei [1 ]
Frosch, Matthew P. [3 ]
Waeber, Christian [1 ]
Ayata, Cenk [1 ,5 ,6 ]
Moskowitz, Michael A. [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA
[2] Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Charlestown, MA 02129 USA
[3] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA
[4] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA
[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Charlestown, MA 02129 USA
[6] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA 02129 USA
关键词
TO-LEFT SHUNT; ISCHEMIC-STROKE; HEMIPLEGIC MIGRAINE; IMAGING FINDINGS; CONTROLLED TRIAL; CLOSURE; PREVALENCE; BRAIN; RISK; MRI;
D O I
10.1002/ana.21871
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Patent foramen ovale and pulmonary arteriovenous shunts are associated with serious complications such as cerebral emboli, stroke, and migraine with aura. The pathophysiological mechanisms that link these conditions are unknown. We aimed to establish a mechanism linking microembolization to migraine aura in an experimental animal model. Methods: We introduced particulate or air microemboli into the carotid circulation in mice to determine whether transient microvascular occlusion, insufficient to cause infarcts, triggered cortical spreading depression (CSD), a propagating slow depolarization that underlies migraine aura. Results: Air microemboli reliably triggered CSD without causing infarction. Polystyrene microspheres (10 km) or cholesterol crystals (<70 mu m) triggered CSD in 16 of 28 mice, with 60% of the mice (40% of those with CSD) showing no infarcts or inflammation on detailed histological analysis of serial brain sections. No evidence of injury was detected on magnetic resonance imaging examination (9.4T; T2 weighted) in 14 of 15 selected animals. The occurrence of CSD appeared to be related to the magnitude and duration of flow reduction, with a triggering mechanism that depended on decreased brain perfusion but not sustained tissue damage. Interpretation: In a mouse model, microemboli triggered CSD, often without causing microinfarction. Paradoxical embolization then may link cardiac and extracardiac right-to-left shunts to migraine aura. If translatable to humans, a subset of migraine auras may belong to a spectrum of hypoperfusion disorders along with transient ischemic attacks and silent infarcts. ANN NEUROL 2010;67:221-229
引用
收藏
页码:221 / 229
页数:9
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