title: Pearls and pitfalls in experimental models of spreading depression.
abstract: BACKGROUND
  Spreading depression (SD) is the electrophysiological substrate of migraine aura and a potential trigger for headache. Since its discovery by Leão in 1944, SD has transformed from being viewed as an epiphenomenon into a therapeutic target relevant in the pathophysiology of migraine and brain injury.
  
  
  OBJECTIVE
  Despite decades of research, the underpinnings of SD are still poorly understood, hampering our efforts to selectively block its initiation and spread. Experimental models have nevertheless been useful to measure the likelihood of SD occurrence (i.e. SD susceptibility) and characterize genetic, physiological and pharmacological modulation of SD in search of potential therapies, such as in migraine prophylaxis and stroke. Here, I review experimental SD susceptibility endpoints and surrogates, and minimum essential model requirements to improve their utility in drug screening.
  
  
  CONCLUSIONS
  A critical reappraisal of strengths and caveats of experimental models of SD susceptibility is needed to set standards and improve data quality, interpretation and reconciliation.
authors.affiliation: Neurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, MA 02129, USA. cayata@partners.org
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D013181:Cortical Spreading Depression; D004195:Disease Models, Animal; D006801:Humans; D020325:Migraine with Aura / Q000188:drug therapy* / Q000503:physiopathology*; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology*
keywords: Spreading depression; animal models; aura; migraine