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This phenomenon is believed to underlie the migraine aura and similar waves of depolarization may exacerbate injury in a number of neurological disease states. CSD is characterized by massive ion dyshomeostasis, cell swelling, and multiphasic blood flow changes. Recently, it was shown that CSD is associated with a closure of the paravascular space (PVS), a proposed exit route for brain interstitial fluid and solutes, including excitatory and inflammatory substances that increase in the wake of CSD. The PVS closure was hypothesized to rely on swelling of astrocytic endfeet due to their high expression of aquaporin\u20104 (AQP4) water channels. We investigated whether CSD is associated with swelling of endfeet around penetrating arterioles in the cortex of living mice. Endfoot cross\u2010sectional area was assessed by two\u2010photon microscopy of mice expressing enhanced green fluorescent protein in astrocytes and related to the degree of arteriolar constriction. In anesthetized mice CSD triggered pronounced endfoot swelling that was short\u2010lasting and coincided with the initial arteriolar constriction. Mice lacking AQP4 displayed volume changes of similar magnitude. CSD\u2010induced endfoot swelling and arteriolar constriction also occurred in awake mice, albeit with faster kinetics than in anesthetized mice. We conclude that swelling of astrocytic endfeet is a robust event in CSD. The early onset and magnitude of the endfoot swelling is such that it may significantly delay perivascular drainage of interstitial solutes in neurological conditions where CSD plays a pathophysiological role.<\/jats:p>","DOI":"10.1002\/glia.23604","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T13:39:36Z","timestamp":1550756376000},"page":"1113-1121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Aquaporin\u20104\u2010independent volume dynamics of astroglial endfeet during cortical spreading depression"],"prefix":"10.1002","volume":"67","author":[{"given":"Alexander Brana","family":"Rosic","sequence":"first","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didrik B.","family":"Dukefoss","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut Sindre","family":"\u00c5bj\u00f8rsbr\u00e5ten","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wannan","family":"Tang","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidar","family":"Jensen","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Petter","family":"Ottersen","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"},{"name":"Office of the President Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-7117","authenticated-orcid":false,"given":"Rune","family":"Enger","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"},{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-4362","authenticated-orcid":false,"given":"Erlend A.","family":"Nagelhus","sequence":"additional","affiliation":[{"name":"GliaLab and Letten Centre, Division of Physiology, Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo  Oslo Norway"},{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1812-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102409360828"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38635"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2014"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0273-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012867108"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.192"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12727"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.04.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw359"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv054"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16654495"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-11-26"},{"key":"e_1_2_6_16_1","first-page":"37","article-title":"Metabolite clearance during wakefulness and sleep","volume":"2017","author":"Hladky S. 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