20.500.12556/RUL-185534 Dose-dependent reduction of optic nerve sheath diameter during graded lower body negative pressure in healthy adults of both sexes Background: 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.Methods: Forty-four healthy young adults (22 female, 22 male) underwent graded LBNP (−10 to −40 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 mm 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.Results: A progressive and statistically significant reduction in ONSD was observed at every LBNP level in both sexes. Female participants showed reductions of approximately −4.4 % (LBNP10, p = 0.001), −9.1 % (LBNP20, p < 0.001), −13.2 % (LBNP30, p < 0.001) and −15.9 % (LBNP40, p < 0.001) relative to supine baseline. Male-specific contrasts showed comparable reductions (LBNP10: −3.0 %, p = 0.022; LBNP20: −7.9 %, p < 0.001; LBNP30: −10.1 %, p < 0.001; LBNP40: −13.4 %, p < 0.001). The main effect of sex was not significant (p = 1.00), and no state × sex interaction reached significance (all p > 0.1). ONSD returned to baseline during recovery (female: p = 0.173; male: p = 0.059).Conclusion: Graded LBNP induces a progressive, dose-dependent reduction in ONSD that is detectable already at mild LBNP (−10 mmHg) and reaches approximately −15 % at −40 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. cardiovascular physiology central hypovolemia intracranial pressure lower body negative pressure network physiology optic nerve sheath diameter sex differences ultrasound microgravity kardiovaskularna fiziologija centralna hipovolemija intrakranialni tlak negativni tlak spodnjega dela telesa premer ovojnice vidnega živca spolne razlike transorbitalna ultrasonografija mikrogravitacija true false true Angleški jezik Slovenski jezik Članek v reviji 2026-08-07 15:05:09 2026-08-07 15:05:21 2026-08-08 04:08:09 0000-00-00 00:00:00 2026 0 0 11 str. Vol. 6, art. 1908460 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 531.5:612.819 2674-0109 10.3389/fnetp.2026.1908460 287272195 Bergauer_..._Dose-dependent....pdf Bergauer_..._Dose-dependent....pdf 1 6C54C9AEA4BE74C57F59B44C983B23E5 c750e245b97d361c9e2c4be561341075f3934de1149cce55292257dde97ef915 20d0a7fb-9261-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244156 https://www.frontiersin.org/journals/network-physiology/articles/10.3389/fnetp.2026.1908460/full 1 4e7c5743-9260-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244155 Fakulteta za strojništvo 0 0 0