{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T17:17:59Z","timestamp":1770225479592,"version":"3.49.0"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T00:00:00Z","timestamp":1583884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5R01GM084979"],"award-info":[{"award-number":["5R01GM084979"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1R01AG061447"],"award-info":[{"award-number":["1R01AG061447"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0229156","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T13:24:49Z","timestamp":1583933089000},"page":"e0229156","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Intranasal administration of dantrolene increased brain concentration and duration"],"prefix":"10.1371","volume":"15","author":[{"given":"Jintao","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuchun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingcheng","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryellen F.","family":"Eckenhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-8378","authenticated-orcid":true,"given":"Huafeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,3,11]]},"reference":[{"issue":"4","key":"pone.0229156.ref001","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1097\/ALN.0b013e318167aee2","article-title":"Cardiac arrests and deaths associated with malignant hyperthermia in north america from 1987 to 2006: a report from the north american malignant hyperthermia registry of the malignant hyperthermia association of the United States","volume":"108","author":"MG Larach","year":"2008","journal-title":"Anesthesiology"},{"issue":"4","key":"pone.0229156.ref002","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF03004694","article-title":"Malignant hyperthermia: a statistical review","volume":"17","author":"BA Britt","year":"1970","journal-title":"Can Anaesth Soc J"},{"key":"pone.0229156.ref003","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.brainresbull.2016.02.018","article-title":"Ryanodine receptors contribute to the induction of ischemic tolerance","volume":"122","author":"E Nakamura-Maruyama","year":"2016","journal-title":"Brain Res Bull"},{"issue":"7","key":"pone.0229156.ref004","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1055\/s-2008-1038731","article-title":"Can dantrolene protect spinal cord against ischemia\/reperfusion injury? An experimental study","volume":"56","author":"CU Kocogullari","year":"2008","journal-title":"Thorac Cardiovasc Surg"},{"key":"pone.0229156.ref005","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1750-1326-6-81","article-title":"Dantrolene is neuroprotective in Huntington's disease transgenic mouse model","volume":"6","author":"X Chen","year":"2011","journal-title":"Mol Neurodegener"},{"key":"pone.0229156.ref006","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neuroscience.2012.06.050","article-title":"Dantrolene Is Neuroprotective in Vitro, but Does Not Affect Survival in Sod1(G93a) Mice","volume":"220","author":"KA Staats","year":"2012","journal-title":"Neuroscience"},{"issue":"8","key":"pone.0229156.ref007","first-page":"4617","article-title":"Effects of methylprednisolone, dantrolene, and their combination on experimental spinal cord injury","volume":"7","author":"IR Rosado","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"issue":"9","key":"pone.0229156.ref008","first-page":"555","article-title":"Dantrolene: A selective ryanodine receptor antagonist, protects against pentylenetetrazole-induced seizure in mice","volume":"54","author":"M Keshavarz","year":"2016","journal-title":"Acta Medica Iranica"},{"issue":"7","key":"pone.0229156.ref009","doi-asserted-by":"crossref","first-page":"e68809","DOI":"10.1371\/journal.pone.0068809","article-title":"Disruption of calcium homeostasis in cardiomyocytes underlies cardiac structural and functional changes in severe sepsis","volume":"8","author":"MR Celes","year":"2013","journal-title":"PLoS One"},{"issue":"12","key":"pone.0229156.ref010","doi-asserted-by":"crossref","first-page":"e52056","DOI":"10.1371\/journal.pone.0052056","article-title":"Stabilizing ER Ca2+ channel function as an early preventative strategy for Alzheimer\u2019s disease","volume":"7","author":"S Chakroborty","year":"2012","journal-title":"PloS one"},{"issue":"4","key":"pone.0229156.ref011","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1016\/j.jalz.2011.09.141","article-title":"Early and chronic treatment with dantrolene blocked later learning and memory deficits in older Alzheimer's triple transgenic mice","volume":"7","author":"J Peng","year":"2011","journal-title":"Alzheimers Dement"},{"issue":"34","key":"pone.0229156.ref012","doi-asserted-by":"crossref","first-page":"11820","DOI":"10.1523\/JNEUROSCI.0875-12.2012","article-title":"Ryanodine receptor blockade reduces amyloid-beta load and memory impairments in Tg2576 mouse model of Alzheimer disease","volume":"32","author":"B Oules","year":"2012","journal-title":"J Neurosci"},{"issue":"12","key":"pone.0229156.ref013","doi-asserted-by":"crossref","first-page":"e52056","DOI":"10.1371\/journal.pone.0052056","article-title":"Stabilizing ER Ca(2+) Channel Function as an Early Preventative Strategy for Alzheimer's Disease","volume":"7","author":"S Chakroborty","year":"2012","journal-title":"PLoS One"},{"issue":"4","key":"pone.0229156.ref014","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jnnp.44.4.334","article-title":"The effect of dantrolene sodium in relation to blood levels in spastic patients after prolonged administration","volume":"44","author":"WJ Meyler","year":"1981","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"pone.0229156.ref015","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1600-0773.1989.tb00621.x","article-title":"Whole-body autoradiography of 14C-dantrolene in the marmoset monkey","volume":"64","author":"EW Wuis","year":"1989","journal-title":"BMC Pharmacol Toxicol"},{"issue":"7","key":"pone.0229156.ref016","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.addr.2011.11.002","article-title":"Intranasal delivery of biologics to the central nervous system","volume":"64","author":"JJ Lochhead","year":"2012","journal-title":"Adv Drug Deliv Rev"},{"issue":"12","key":"pone.0229156.ref017","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1111\/j.2042-7158.2012.01555.x","article-title":"Intranasal delivery of insulin via the olfactory nerve pathway","volume":"64","author":"DB Renner","year":"2012","journal-title":"J Pharm Pharmacol"},{"issue":"3","key":"pone.0229156.ref018","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuroscience.2008.01.013","article-title":"Delivery of interferon-\u03b2 to the monkey nervous system following intranasal administration","volume":"152","author":"R Thorne","year":"2008","journal-title":"Neuroscience"},{"issue":"4","key":"pone.0229156.ref019","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"Intranasal delivery to the central nervous system: mechanisms and experimental considerations","volume":"99","author":"SV Dhuria","year":"2010","journal-title":"J Pharm Sci"},{"issue":"3","key":"pone.0229156.ref020","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/WAD.0000000000000075","article-title":"Long-term dantrolene treatment reduced intraneuronal amyloid in aged Alzheimer triple transgenic mice","volume":"29","author":"Z Wu","year":"2015","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"3","key":"pone.0229156.ref021","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1124\/jpet.111.180398","article-title":"Quantitative evaluation of the impact of active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier on the predictability of the unbound concentrations of drugs in the brain using cerebrospinal fluid concentration as a surrogate","volume":"339","author":"H Kodaira","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"pone.0229156.ref022","article-title":"Simple behavioral assessment of mouse olfaction","author":"M Yang","year":"2009","journal-title":"Curr Protoc Neurosci"},{"issue":"2","key":"pone.0229156.ref023","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neulet.2012.04.008","article-title":"Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice","volume":"516","author":"J Peng","year":"2012","journal-title":"Neurosci Lett"},{"issue":"10","key":"pone.0229156.ref024","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1124\/dmd.114.058545","article-title":"Brain penetration of WEB 2086 (Apafant) and dantrolene in Mdr1a (P-glycoprotein) and Bcrp knockout rats","volume":"42","author":"H Fuchs","year":"2014","journal-title":"Drug Metab Dispos"},{"issue":"6","key":"pone.0229156.ref025","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1046\/j.1471-4159.1996.67062390.x","article-title":"Dantrolene is cytoprotective in two models of neuronal cell death","volume":"67","author":"H Wei","year":"1996","journal-title":"J Neurochem"},{"issue":"48","key":"pone.0229156.ref026","doi-asserted-by":"crossref","first-page":"12713","DOI":"10.1523\/JNEUROSCI.3909-08.2008","article-title":"Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3","volume":"28","author":"X Chen","year":"2008","journal-title":"J Neurosci"},{"issue":"12","key":"pone.0229156.ref027","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s11095-005-8384-4","article-title":"BCRP transports dipyridamole and is inhibited by calcium channel blockers","volume":"22","author":"Y Zhang","year":"2005","journal-title":"Pharm Res"},{"issue":"2","key":"pone.0229156.ref028","first-page":"130","article-title":"A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity","volume":"32","author":"A Ward","year":"1986","journal-title":"Drugs"},{"issue":"4","key":"pone.0229156.ref029","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1365-2044.2004.03658.x","article-title":"Dantrolene\u2014a review of its pharmacology, therapeutic use and new developments","volume":"59","author":"T Krause","year":"2004","journal-title":"Anaesthesia"},{"issue":"6","key":"pone.0229156.ref030","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1213\/ANE.0b013e3181f7181c","article-title":"The cytoprotective effects of dantrolene: a ryanodine receptor antagonist","volume":"111","author":"S Inan","year":"2010","journal-title":"Anesth Analg"},{"issue":"7","key":"pone.0229156.ref031","doi-asserted-by":"crossref","first-page":"P597","DOI":"10.1016\/j.jalz.2019.06.2476","article-title":"INTRANASAL DANTROLENE AS A DISEASE-MODIFYING DRUG IN ALZHEIMER 5XFAD MICE","volume":"15","author":"Y Shi","year":"2019","journal-title":"Alzheimers Dement"},{"key":"pone.0229156.ref032","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.expneurol.2013.08.006","article-title":"Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats","volume":"249","author":"Z Wang","year":"2013","journal-title":"Exp Neurol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T13:25:15Z","timestamp":1583933115000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229156"}},"subtitle":[],"editor":[{"given":"Daqing","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,3,11]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0229156","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,11]]}}}