{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:07:02Z","timestamp":1789132022017,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>This hypothesis-driven narrative review synthesizes physiological, clinical, and neuroimaging evidence to advance an integrated pulmonary\u2013cerebral framework for decompression illness (DCI) in repetitive breath-hold diving. Three unresolved features are addressed: the predominance of cerebral involvement, the characteristic localization of lesions to external watershed and distal arterial territories, and the gradual evolution of neurological deficits. Drawing on converging evidence from pulmonary vascular physiology and cerebral gas kinetics, we propose that venous nitrogen bubbles generated during repetitive dives intermittently bypass pulmonary filtration through transient recruitment of intrapulmonary arteriovenous anastomoses (IPAVA), providing a plausible route for episodic arterialization. Once lodged in distal cerebral arteries, these bubbles may enlarge through diffusion of nitrogen from supersaturated brain tissue, potentially contributing to progressive vascular obstruction, endothelial activation, blood\u2013brain barrier disruption, and vasogenic edema. This review articulates a hypothesis-generating integrative framework in which IPAVA-mediated arterialization and diffusion-driven bubble enlargement may together provide a plausible physiological interpretation for the progressive, watershed-predominant cerebral injury unique to repetitive breath-hold diving. Although direct evidence remains limited\u2014particularly regarding dynamic IPAVA behavior and quantitative nitrogen kinetics\u2014 the available data appear broadly compatible with a proposed mechanism centered on episodic arterialization followed by diffusion-driven bubble growth. By framing breath-hold diving\u2013related DCI as a coupled pulmonary\u2013cerebral process, this review proposes a testable conceptual foundation for future integrative research aimed at clarifying IPAVA dynamics, cerebral microvascular vulnerability, and nitrogen transport within supersaturated tissues.<\/jats:p>","DOI":"10.3389\/fphys.2026.1911448","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:14:31Z","timestamp":1789128871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A hypothesis-driven pulmonary\u2013cerebral mechanistic framework of neurological decompression illness in repetitive breath-hold diving"],"prefix":"10.3389","volume":"17","author":[{"given":"Kiyotaka","family":"Kohshi","sequence":"first","affiliation":[{"name":"Division of Neurosurgery, Nishinihon Hospital","place":["Kumamoto, Japan"]},{"name":"Department of Environmental Medicine, Kurume University School of Medicine","place":["Kurume, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Tamaki","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, Kurume University School of Medicine","place":["Kurume, Japan"]},{"name":"Division of Surgery and General Medicine, Tamaki Hospital","place":["Yamaguchi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Morimatsu","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, Kurume University School of Medicine","place":["Kurume, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ishitake","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, Kurume University School of Medicine","place":["Kurume, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Lema\u00eetre","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences, University of Rouen","place":["Mont-Saint-Aignan, France"]},{"name":"CRIOBE USR 3278, CNRS-EPHE-UPVD, PSL","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1002\/ccr3.1479","article-title":"Two episodes of Taravana syndrome in a breath-hold diver with hyperhomocysteinemia","volume":"6","author":"Accurso","year":"2018","journal-title":"Clin. 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