Altered Permeability Of The Blood‐CSF Barrier In Chronic Migraine

Abstract

BackgroundMolecular communication from blood circulation to brain is tightly regulated at multiple biological barriers, but is disrupted in a variety of diseases, disorders, and infections. Recent human and animal data in migraine research has shown conflicting results regarding barrier disruption. These contradictions require resolution because a leaky barrier will expose the brain to potentially harmful components with diverse deleterious effects on brain function.MethodsSince blood‐to‐CSF transfer studies have not yet been performed in migraineurs, we studied surrogate biomarkers of barrier disruption in blood and CSF from non‐headache suffering controls and chronic migraine sufferers.ResultsWhen compared to controls, study participants with chronic migraine had clear evidence of barrier leak based on their higher CSF—blood albumin ratio, CSF fibrinogen levels, and CSF levels of the pericyte biomarker, soluble platelet‐derived growth factor receptor β. To test if other blood components were leaking through this barrier, we examined how CSF and blood lipids relate to the CSF—blood albumin ratio. The CSF—blood ratios of trans palmitoleic acid, linoleic acid, and ceramide were higher in chronic migraine and these lipid ratios correlated significantly with the CSF—blood albumin index, consistent with their derivation, at least partly, from a leaking barrier.ConclusionWe conclude that individuals with chronic migraine have distinct disruption of central nervous system (CNS) barriers that allows leakage into the CNS of multiple blood components, including proteins and lipids, and which likely results from, and contributes to the pathophysiology of migraine. The blood‐brain barrier and molecules that leak into the CNS are potential treatment targets.Support or Funding InformationThe National Institutes of Health, R01 NS043295, Higgins Family TrustsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.