{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:14:40Z","timestamp":1792815280521,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,12,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Glyceryl trinitrate (GTN), also known as nitroglycerin, is predominantly recognized as a vasodilator for ischemic heart disease, and its potential neuroprotective properties in acute ischemic stroke remain under exploration. We sought to discover the therapeutic advantages and mechanisms of post\u2010recanalization GTN administration in acute ischemic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">A total of 118 male Sprague\u2013Dawley rats were divided into groups: sham, transient\/permanent middle cerebral artery occlusion (MCAO) with or without GTN treatment, and transient\/permanent MCAO treated with both GTN and KT5823, an inhibitor of PKG. Acute ischemic stroke was induced by transient MCAO for 2\u2009hours followed by 6 or 24\u2009hours of reperfusion and permanent MCAO (28\u2010hour MCAO without reperfusion). The study assessed infarct volumes, neurological deficits, glucose metabolism metrics, NO, and cGMP levels via ELISA. mRNA and protein expression of key molecules of hyperglycolysis, gluconeogenesis, endoplasmic reticulum stress as well as signaling molecules (PKG, AMPK) were conducted via reverse transcription polymerase chain reaction and Western blotting, and cell death was assessed with TUNEL and ELISA. GTN significantly reduced cerebral infarct volumes, neurological deficits, and cell death only after transient MCAO. GTN led to a significant reduction in the expression of NO and cGMP levels, key glucose metabolism, endoplasmic reticulum stress\u2010related genes and proteins, and phosphorylated AMPK while boosting PKG expression, in transient MCAO but not permanent MCAO. The GTN\u2010induced reduction in glucose metabolites, lactate, and reactive oxygen species was exclusive to transient MCAO groups. Coadministration of GTN and PKG inhibitors reversed the observed GTN benefits.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">GTN induced neuroprotection in transient MCAO by improving glucose metabolism and potentially controlling endoplasmic reticulum stress through the NO\u2010cGMP\u2010PKG signaling cascade to inhibit AMPK phosphorylation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.035382","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T11:36:37Z","timestamp":1732275397000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Neuroprotective Potential of Nitroglycerin in Ischemic Stroke: Insights into Neural Glucose Metabolism and Endoplasmic Reticulum Stress Inhibition"],"prefix":"10.1161","volume":"13","author":[{"given":"Shangqian","family":"Jiang","sequence":"first","affiliation":[{"name":"Neuroscience Institute, Beijing Luhe Hospital Capital Medical University Beijing China"},{"name":"Department of Neurology, Beijing Luhe Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-1660","authenticated-orcid":false,"given":"Yuchuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Wayne State University School of Medicine Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongrui","family":"Wang","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Beijing Luhe Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3248-3545","authenticated-orcid":false,"given":"Enoch","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Wayne State University School of Medicine Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Geng","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Beijing Luhe Hospital Capital Medical University Beijing China"},{"name":"Department of Neurology, Beijing Luhe Hospital Capital Medical University Beijing China"},{"name":"Department of Neurosurgery Wayne State University School of Medicine Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4103\/bc.bc_9_24"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4103\/bc.bc_70_22"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc1510178"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.09.1064"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61121-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.001301"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-060211"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00333-7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4103\/bc.bc_52_22"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4103\/bc.bc_31_23"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1179\/1743132813Y.0000000209"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.629576"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.006994"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02542-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4103\/bc.bc_37_23"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2016-012793"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(07)82024-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415061"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000223024.02939.1e"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30194-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2020.179"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.293129"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00802"},{"key":"e_1_3_2_25_2","article-title":"Cerebral gluconeogenesis and diseases","volume":"7","author":"Yip J","year":"2016","unstructured":"Yip J, Geng X, Shen J, Ding Y. 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