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The observed robustness in O\n                    <jats:sub>2<\/jats:sub>\n                    supply was attributed to overcapacity in convective oxygen transport in the pial arterial network combined with a surplus in the number of capillary flow paths. Microcirculatory flux analysis suggests that\n                    <jats:italic toggle=\"yes\">network<\/jats:italic>\n                    induced hemodynamic flow patterns impart\n                    <jats:italic toggle=\"yes\">intrinsic reserve<\/jats:italic>\n                    to protect the brain against perfusion variances or metabolic demand surges during activation. Furthermore, oxygen transport in cortical tissue is characterized by two regimes: in the\n                    <jats:italic toggle=\"yes\">transport zone\u2014<\/jats:italic>\n                    centered on\n                    <jats:italic toggle=\"yes\">penetrating arteriole trees<\/jats:italic>\n                    composed of a single penetrating vessel connected to the post-arteriole capillary transition zone\u2014strong diffusion supports high oxygen tension with only modest contribution from capillaries. This regime transitions into the\n                    <jats:italic toggle=\"yes\">terminal\/reactive zone<\/jats:italic>\n                    where oxygenation is sensitive to capillary density and perfusion. Quasi-dynamic simulations also enabled reconstruction of the BOLD signal underlying functional imaging. Simulations at single micron resolution further show that age-related reductions in arterial saturation and systemic hematocrit were sufficient to induce hypoxic tissue pockets in the terminal zone at nominal perfusion (CBF) and metabolic activity (CMRO\n                    <jats:sub>2<\/jats:sub>\n                    ), and neutrophil adhesion induced capillary flow stalling further exacerbates hypoxia.\n                  <\/jats:p>","DOI":"10.1177\/0271678x251410034","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:29:05Z","timestamp":1773224945000},"page":"1915-1929","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Microvascular network organization and hemodynamic perfusion protect the brain against hypoxia"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9951-0712","authenticated-orcid":false,"given":"Thomas","family":"Ventimiglia","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Lesage","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Polytechnique Montreal, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-630X","authenticated-orcid":false,"given":"Andreas A","family":"Linninger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois Chicago, Chicago, IL, USA"},{"name":"Department of Neurosurgery, University of Illinois Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.136"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26543-w"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20914179"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108260"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0329-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001839"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1963.tb02652.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.153"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-013-0828-0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12156"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16671146"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27534-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60208"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010166"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2025.110014"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3426"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.02.006"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12845"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006549"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008584"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cnm.3735"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-58519-7_5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3278"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12687"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.123.228103"},{"key":"e_1_3_3_27_2","first-page":"4","article-title":"The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves","volume":"40","author":"Hill AV.","year":"1910","unstructured":"Hill AV. 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