{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:23Z","timestamp":1786121363390,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"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. Netw. Physiol."],"abstract":"\n Background<\/jats:title>\n Optic nerve sheath diameter (ONSD) measured by ultrasound provides a non-invasive surrogate of intracranial pressure. Although lower body negative pressure (LBNP) is widely used to simulate central hypovolemia, the dose-response relationship between graded LBNP and ONSD, and possible sex differences therein, are incompletely characterized.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Forty-four healthy young adults (22 female, 22 male) underwent graded LBNP (\n \n \n \n \u2212<\/mml:mo>\n 10<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n to\n \n \n \n \u2212<\/mml:mo>\n 40<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mmHg) in the supine position; valid ONSD data were available in 37 participants (18 female, 19 male) who constituted the analytical sample. ONSD was measured from transbulbar B-mode ultrasound images 3\u00a0mm posterior to the globe, with three representative frames averaged per condition. Relative changes from individual supine baseline were analyzed using a linear mixed-effects model with state, sex, and their interaction as fixed effects.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A progressive and statistically significant reduction in ONSD was observed at every LBNP level in both sexes. Female participants showed reductions of approximately\n \n \n \n \u2212<\/mml:mo>\n 4.4<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n (LBNP10, p = 0.001),\n \n \n \n \u2212<\/mml:mo>\n 9.1<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n (LBNP20, p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001),\n \n \n \n \u2212<\/mml:mo>\n 13.2<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n (LBNP30, p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001) and\n \n \n \n \u2212<\/mml:mo>\n 15.9<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n (LBNP40, p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001) relative to supine baseline. Male-specific contrasts showed comparable reductions (LBNP10:\n \n \n \n \u2212<\/mml:mo>\n 3.0<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n , p = 0.022; LBNP20:\n \n \n \n \u2212<\/mml:mo>\n 7.9<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n , p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001; LBNP30:\n \n \n \n \u2212<\/mml:mo>\n 10.1<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n , p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001; LBNP40:\n \n \n \n \u2212<\/mml:mo>\n 13.4<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n , p\n \n \n \n <<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.001). The main effect of sex was not significant (p = 1.00), and no state\n \n \n \n \u00d7<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n sex interaction reached significance (all p\n \n \n \n ><\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n 0.1). ONSD returned to baseline during recovery (female: p = 0.173; male: p = 0.059).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Graded LBNP induces a progressive, dose-dependent reduction in ONSD that is detectable already at mild LBNP (\n \n \n \n \u2212<\/mml:mo>\n 10<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mmHg) and reaches approximately\n \n \n \n \u2212<\/mml:mo>\n 15<\/mml:mn>\n %<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n at\n \n \n \n \u2212<\/mml:mo>\n 40<\/mml:mn>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n mmHg. No statistically significant sex-related differences in the ONSD response to graded LBNP were detected in the present study. These findings support the use of transbulbar ONSD ultrasound as a sensitive non-invasive marker consistent with intracranial-pressure reductions during simulated central hypovolemia. By linking a systemic cardiovascular perturbation to a cerebro-ocular pressure readout, the study offers a network-physiology view of central-hypovolemia responses relevant to spaceflight and orthostatic-stress research.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fnetp.2026.1908460","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:22:33Z","timestamp":1786076553000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-dependent reduction of optic nerve sheath diameter during graded lower body negative pressure in healthy adults of both sexes"],"prefix":"10.3389","volume":"6","author":[{"given":"Andrej","family":"Bergauer","sequence":"first","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz","place":["Graz, Austria"]},{"name":"Department of Surgery, General Hospital (LKH S\u00fcdweststeiermark)","place":["Wagna, Austria"]},{"name":"Faculty of Mechanical Engineering, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janez","family":"Urevc","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical Engineering, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Steuber","sequence":"additional","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz","place":["Graz, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schmid-Zalaudek","sequence":"additional","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz","place":["Graz, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vid","family":"Pivec","sequence":"additional","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz","place":["Graz, Austria"]},{"name":"Department of Surgery, General Hospital (LKH S\u00fcdweststeiermark)","place":["Wagna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandu","family":"Goswami","sequence":"additional","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center of Vascular Biology, Immunity and Inflammation, Medical University of Graz","place":["Graz, Austria"]},{"name":"Center for Space and Aviation Health, Mohammed Bin Rashid University of Medicine and Health Sciences","place":["Dubai, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s12028-019-00853-x","article-title":"A proposal for a new protocol for sonographic assessment of the optic nerve sheath diameter: the closed protocol","volume":"32","author":"Aspide","year":"2020","journal-title":"Neurocrit. 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