Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

• DOI: 10.1523/jneurosci.3390-16.2017
• Publication Date: 2017-02-14T01:40:28Z
• Authors: Aaron J. Schain; Agustin Melo-Carr...; Andrew M. Strassman; Rami Burstein
• Keywords: Glymphatic System; Cortical Spreading Depression; Clearance

Functioning of the glymphatic system, a network paravascular tunnels through which cortical interstitial solutes are cleared from brain, has recently been linked to sleep and traumatic brain injury, both can affect progression migraine. This led us investigate connection between migraine system. Taking advantage novel in vivo method we developed using two-photon microscopy visualize space (PVS) naive uninjected mice, show that single wave spreading depression (CSD), an animal model aura, induces rapid nearly complete closure PVS around surface as well penetrating arteries veins lasting several minutes, gradually recovering over 30 min. A temporal mismatch constriction or dilation blood vessel lumen suggests this is not likely result changes diameter. We also CSD impairs flow, indicated by reduced rate at intraparenchymally injected dye was cortex PVS. first observation with abnormal event underlies neurological disorder. More specifically, findings demonstrate link system migraine, suggest mechanism for regulation flow. SIGNIFICANCE STATEMENT Impairment solute clearance described prolonged wakefulness, aging. paper shows depression, neural correlate closes holds potential define It implicates altered endothelial functioning brain.