{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:01:17Z","timestamp":1781704877291,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Medical and Health Appropriate Technology Development and Application Project","award":["S2022091"],"award-info":[{"award-number":["S2022091"]}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2020GXNSFAA259053"],"award-info":[{"award-number":["2020GXNSFAA259053"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2015GXNSFAA139171"],"award-info":[{"award-number":["2015GXNSFAA139171"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260241"],"award-info":[{"award-number":["82260241"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangxi Key Research and Development Project","award":["AB24010094"],"award-info":[{"award-number":["AB24010094"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Moyamoya disease (MMD) is characterized by progressive stenosis of the internal carotid artery and compensatory moyamoya angiogenesis. Although multiple studies have identified\n                      <jats:italic>GUCY1A3<\/jats:italic>\n                      (encoding the \u03b11 subunit of soluble guanylate cyclase) as a susceptibility gene for MMD, genome\u2011wide association studies (GWAS) have not yet established it as a significant locus. To address this discrepancy, this study used\n                      <jats:italic>Gucy1a3<\/jats:italic>\n                      loss\u2011of\u2011function mice (\n                      <jats:italic>Gucy1a3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) to investigate the potential causal relationship between\n                      <jats:italic>GUCY1A3<\/jats:italic>\n                      loss\u2011of\u2011function and the cerebrovascular phenotype in MMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Intracranial arterial anatomy was assessed using 7.0T high\u2011resolution magnetic resonance angiography (MRA) and cerebral vascular casting. Vasoconstrictive remodeling was evaluated by calculating diameter ratios \u2013 specifically, internal carotid artery (ICA)\/basilar artery (BA) and middle cerebral artery (MCA)\/BA ratios. Histopathological evaluation was performed using hematoxylin and eosin (H&amp;amp;E) staining, elastic van Gieson (EVG) staining, and \u03b1\u2011smooth muscle actin (\u03b1\u2011SMA) immunohistochemistry to assess intracerebral macrovascular pathology. Cortical microvascular density and caliber were quantified using CD31 immunohistochemistry, while leptomeningeal vascular architecture was systematically analyzed using vascular casting, followed by skeletonization and topological analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Gucy1a3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      developed normally, with no significant differences in intracranial vascular anatomy, diameter ratios, or large\u2011vessel histopathology compared to wild\u2011type mice (Wt). However, the leptomeningeal vascular network in\n                      <jats:italic>Gucy1a3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      exhibited significant simplification, characterized by reduced vascular branching (365.90 \u00b1 14.92 versus 330.00 \u00b1 9.72,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0003) and density (total junctions, 174.10 \u00b1 10.43 versus 155.80 \u00b1 11.39,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0101; Vascular area%, 29.57 \u00b1 4.40 versus 20.75 \u00b1 2.01,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0021). In addition, cortical microvessel density (vascular density\/ mm2, 515.70 \u00b1 15.53 versus 351.20 \u00b1 80.69,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0022; area%, 0.83 \u00b1 0.20 versus 0.44 \u00b1 0.18,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0152) and average diameter (3.5mm versus 2.5mm) were significantly reduced in\n                      <jats:italic>Gucy1a3<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Under early adult (8\u201312 weeks) conditions,\n                      <jats:italic>GUCY1A3<\/jats:italic>\n                      deficiency did not produce detectable large\u2011artery stenosis typical of MMD. Instead, it induced a unique cerebrovascular phenotype marked by \u201crarefaction\u201d of both cortical microvessels and leptomeningeal networks. Whether large\u2011vessel pathology develops in aged mice remains to be determined. These findings suggest that\n                      <jats:italic>GUCY1A3<\/jats:italic>\n                      loss\u2011of\u2011function may contribute to MMD susceptibility primarily by compromising small\u2011vessel integrity, necessitating additional triggers for full disease manifestation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1669177","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:48:45Z","timestamp":1776055725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrovascular phenotype analysis in Gucy1a3 loss-of-function mice: insights into moyamoya disease susceptibility"],"prefix":"10.3389","volume":"17","author":[{"given":"Pingkai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University","place":["Nanning, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanghua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, First Affiliated Hospital of Guangxi Medical University","place":["Nanning, 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