Microemboli may link spreading depression, migraine aura, and patent foramen ovale
Article first published online: 14 SEP 2009
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 67, Issue 2, pages 221–229, February 2010
How to Cite
Nozari, A., Dilekoz, E., Sukhotinsky, I., Stein, T., Eikermann-Haerter, K., Liu, C., Wang, Y., Frosch, M. P., Waeber, C., Ayata, C. and Moskowitz, M. A. (2010), Microemboli may link spreading depression, migraine aura, and patent foramen ovale. Ann Neurol., 67: 221–229. doi: 10.1002/ana.21871
- Issue published online: 11 MAR 2010
- Article first published online: 14 SEP 2009
- Accepted manuscript online: 14 SEP 2009 12:00AM EST
- Manuscript Accepted: 1 SEP 2009
- Manuscript Revised: 31 AUG 2009
- Manuscript Received: 22 JUN 2009
- National Institute of Neurological Disorders and Stroke, Massachusetts. Grant Numbers: NS061505, NS35611
- General Hospital Department of Anesthesia
- NIH National Research Service. Grant Number: GM07592
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.
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.
Air microemboli reliably triggered CSD without causing infarction. Polystyrene microspheres (10μm) or cholesterol crystals (<70μm) 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.
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