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Considering that the shared goal of most human CGRP-based neurosensory systems is the protection from an acute threat, especially if hypoxic, what is the end meaning of a migraine attack? In this paper, we have reviewed available evidence on the possible role of the trigemino-vascular system in maintaining cerebral perfusion pressure homeostasis, despite the large physiological fluctuations in intracranial pressure occurring in daily life activities. In this perspective, the migraine attack is presented as the response to a cerebral hypoxic threat consequent to a deranged intracranial pressure control aimed at generating a temporary withdrawal from the environment with limitation of physical activity, a condition required to promote the restoration of cerebral fluids dynamic balance.<\/jats:p>","DOI":"10.1007\/s10072-022-06200-x","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T04:13:19Z","timestamp":1657253599000},"page":"5665-5672","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-8668","authenticated-orcid":false,"given":"Roberto","family":"De Simone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Sansone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Miele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Stornaiuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Braca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"6200_CR1","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1111\/head.13529","volume":"59","author":"S Lyengar","year":"2019","unstructured":"Lyengar S, Johnson KW, Ossipov MH, Aurora SK (2019) CGRP and the trigeminal system in migraine. 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