Translational imaging studies of cortical spreading depression in experimental models for migraine aura

Abstract

This perspective discusses cortical spreading depression (CSD) phenomena and their translational significance for human migraine aura and the peri-infarct events following cerebral ischemia and injury. They begin with interstitial K⁺ release and accumulation following neuronal stimulation, and a buffering astrocytic K⁺ influx and remote liberation propagating waves of neuronal hyperexcitability and depression. Diffusion-weighted echoplanar MRI demonstrates CSD features in gyrencephalic brains recapitulating human migraine aura, spatial and temporal features of single primary events and multiple secondary events, their stimulus dependence, pharmacological properties, and their relationship to blood oxygenation level-dependant signals and late cerebrovascular changes. The article finally explores prospects for physiological studies of CSD gaining fuller insights both into mechanisms underlying the pathology of the corresponding human condition and possible approaches to management.

Keywords::

• cerebral ischemia
• cortical spreading depression
• head injury
• migraine
• MRI

Financial and competing interests disclosure

We thank GlaxoSmithKline, the Biotechnology and Biological Sciences Research Council (BBSRC), the University of Cambridge, the Herchel Smith Endowment, the Medical Research Council (MRC) and the Royal Society and Wellcome Trust for funding support of our research.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.