{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:14:59Z","timestamp":1779963299090,"version":"3.53.1"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K08EY033013"],"award-info":[{"award-number":["K08EY033013"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MH086638"],"award-info":[{"award-number":["R01MH086638"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypoxia is a critical determinant of neuronal function and vulnerability in the brain. While neuronal density has been extensively characterized across cortical regions, the spatial relationship between neurons and the microvasculature represents an additional structural constraint on oxygen diffusion and metabolic support. In particular, the distance between neurons and nearby capillaries influences local oxygen availability required to sustain neuronal activity and maintain ionic homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we quantified neuron\u2013capillary spatial relationships across cortical layers in the human primary visual cortex. Postmortem tissue from three neuropathologically normal individuals (ages 55\u201375\u2009years) was analyzed using dual\u2010label immunohistochemistry for NeuN (neurons) and CD34 (vascular endothelial cells). Regions of interest corresponding to neocortical layers were delineated by a neuropathologist. Automated image analysis in QuPath was used to segment neurons using object\u2010based classification and capillaries using pixel\u2010based classification. Distances between neuronal and vascular centroids were corrected for tissue shrinkage using a linear scaling factor of 1.20. Centroids of segmented objects were extracted, and nearest\u2010neighbor relationships were computed using a quad tree spatial search algorithm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across more than 155\u2009000 neurons and 84\u2009000 vascular objects, we observed a consistent laminar gradient in neuron\u2013capillary distance. Neurons in superficial and deep layers were located farther from capillaries, whereas neurons in the central layers exhibited shorter distances, with layers III and IV demonstrating median distances of ~30\u201345\u2009\u03bcm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that neuron\u2013capillary spatial relationships vary systematically across cortical depth, suggesting that cortical microvascular architecture is consistent with layer\u2010specific metabolic demands.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.70064","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:33:46Z","timestamp":1778740426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Capillary Density and Neuronal Homeostasis in Human Primary Visual Cortex"],"prefix":"10.1111","volume":"33","author":[{"given":"Yi\u2010Chung","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J. H.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health  New Haven Connecticut USA"},{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"McDougal","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yale School of Public Health  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Lytton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University  Brooklyn New York USA"},{"name":"Department of Neurology Kings County Hospital Center  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello M.","family":"DiStasio","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Ophthalmology and Visual Science Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-5562-5_3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023508\u2010y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/BPL\u2010170055"},{"key":"e_1_2_10_5_1","first-page":"18","volume-title":"Frontiers of Neurology and Neuroscience","author":"Tatu L.","year":"2014"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02863881"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab127"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1944.7.6.359"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2333"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00237.2002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306\u20104522(78)90122\u20107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.3.1065"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1902"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15966"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2015.08.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh545"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)03121-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12386"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914722107"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2008.35"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.73"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0082\u201022.2022"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.192"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227737"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017204\u20105"},{"issue":"1","key":"e_1_2_10_27_1","first-page":"13","article-title":"Different Volume Changes of Cerebral Cortex and White Matter During Histological Preparation","volume":"86","author":"Kretschmann H. 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