{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:52:56Z","timestamp":1781844776435,"version":"3.54.5"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Subarachnoid hemorrhage (SAH) is a highly lethal and disabling type of stroke. The main causes of poor prognosis are neuroinflammation, blood\u2013brain barrier (BBB) disruption and brain edema following hemorrhage. Didymin has shown neuroprotective effects in intracerebral hemorrhage; however, its regulatory role in SAH remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The rat SAH model was established using the internal carotid artery puncture method, while an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model was developed by stimulating human brain microvascular endothelial cells (HBMECs) with hemoglobin (Hb). Following didymin treatment, neurological functional outcomes were assessed using the modified Garcia score and the balance beam test. Nissl staining was performed to evaluate neuronal pathological changes. Immunofluorescence staining was employed to assess microglial activation and BBB integrity. Brain water content was measured to evaluate the severity of cerebral edema. Western blot analysis was utilized to detect the expression of matrix metalloproteinase 9 (MMP9), apoptosis-related proteins (Bcl-XL, Bcl-2, Bax), pro-inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ), and tight junction proteins (ZO-1, Occludin).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Didymin treatment significantly improved neurological function scores in SAH rats by alleviating neuronal damage and apoptosis. On one hand, didymin reduced post-SAH neuroinflammation by inhibiting excessive microglial activation and the expression of pro-inflammatory cytokines. On the other hand, didymin preserved BBB integrity and alleviated brain edema by downregulating MMP9 expression. In Hb-induced cell model, didymin suppressed MMP9 expression and promoted the expression of tight junction proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this study, we demonstrated that didymin mitigates neuronal damage and apoptosis following SAH, effectively suppresses neuroinflammation, maintains the integrity of the BBB, and attenuates brain edema. These findings suggest that didymin holds promise as a potential therapeutic candidate for the treatment of SAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1857779","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:28:49Z","timestamp":1781843329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Didymin mitigates neuroinflammation and preserves blood\u2013brain barrier integrity after subarachnoid hemorrhage"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingqiang","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, 3201 Hospital of Xi\u2019an Jiaotong University Health Science Center","place":["Hanzhong, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 3201 Hospital of Xi\u2019an Jiaotong University Health Science Center","place":["Hanzhong, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 3201 Hospital of Xi\u2019an Jiaotong University Health Science Center","place":["Hanzhong, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbing","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 3201 Hospital of Xi\u2019an Jiaotong University Health Science Center","place":["Hanzhong, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/S0140-6736(07)60153-6","article-title":"Subarachnoid haemorrhage","volume":"369","author":"van 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hyperglycemia-induced human umbilical endothelial cells dysfunction and death","volume":"152","author":"Shukla","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"956","DOI":"10.3349\/ymj.2022.0040","article-title":"Didymin alleviates cerebral ischemia-reperfusion injury by activating the PPAR signaling pathway","volume":"63","author":"Li","year":"2022","journal-title":"Yonsei Med J"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"810582","DOI":"10.3389\/fimmu.2022.810582","article-title":"Didymin suppresses microglia Pyroptosis and Neuroinflammation through the Asc\/Caspase-1\/GSDMD pathway following experimental intracerebral hemorrhage","volume":"13","author":"Gu","year":"2022","journal-title":"Front Immunol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/s12974-023-02939-y","article-title":"Ly6C-high monocytes alleviate brain injury in experimental subarachnoid hemorrhage in 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bioavailability of flavonoids: a review","volume":"62","author":"Chen","year":"2022","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"29428","DOI":"10.18632\/oncotarget.15204","article-title":"Didymin: an orally active citrus flavonoid for targeting neuroblastoma","volume":"8","author":"Singhal","year":"2017","journal-title":"Oncotarget"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1080\/10408398.2021.1947772","article-title":"Enhancement of bioavailability and bioactivity of diet-derived flavonoids by application of nanotechnology: a review","volume":"63","author":"Teng","year":"2023","journal-title":"Crit Rev Food Sci Nutr"}],"container-title":["Frontiers in 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