{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:40:46Z","timestamp":1787582446727,"version":"build-2736575974"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":74,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Fluids Barriers CNS"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The blood-brain barrier is a major obstacle drug transport into the central nervous system. High-altitude hypoxia induces structural and functional alterations in the central nervous system, which in turn can influence drug metabolism and transport throughout the body.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Rats and human brain microvascular endothelial cells (hCMEC\/D\n                      <jats:sub>3<\/jats:sub>\n                      ) were used as experimental models in this study. The effects of hypoxia on blood-brain barrier structure and function were assessed using Evans Blue staining and confocal laser scanning microscopy. Changes in the expression and activity of drug transporters and drug-metabolizing enzymes under hypoxic conditions were investigated using data-independent acquisition (DIA) proteomic sequencing, RT-qPCR, and western blot. Additionally, pharmacokinetic studies were conducted to evaluate drug concentrations across the blood-brain barrier.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High-altitude hypoxic environments significantly altered the cerebral distribution and trans-blood-brain barrier transport of drug substrates by upregulating the expression of the efflux transporter, ATP-binding cassette subfamily B member 1 (Abcb1), downregulating the expression of the drug-metabolizing enzyme CYP2B1, and increasing blood-brain barrier permeability. Moreover, the prolonged half-life (t\u2081\/\u2082) and reduced total clearance (CL) observed for drug substrates indicate a significant deceleration in their in vivo metabolism under high-altitude hypoxia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings preliminarily reveal the differential characteristics of drug metabolism under high-altitude hypoxic environments, implying potential differences in drug disposition between high-altitude and plain human populations. Accordingly, these findings provide novel theoretical insights into the molecular regulatory mechanism of drug metabolism in hypoxic plateau environments, and lay a valuable foundational reference for subsequent basic research on rational drug application in plateau areas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12987-026-00829-y","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:03:36Z","timestamp":1781190216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional impact of high-altitude hypoxia on central nervous system drug transport: integrated analysis of blood-brain barrier permeability, drug transporter\/enzyme expression, and pharmacokinetics"],"prefix":"10.1186","volume":"23","author":[{"given":"Guiqin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabin","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delong","family":"Duo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"issue":"2","key":"829_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41569-023-00924-9","volume":"21","author":"JP Richalet","year":"2024","unstructured":"Richalet JP, Hermand E, Lhuissier FJ. Cardiovascular physiology and pathophysiology at high altitude. Nat Rev Cardiol. 2024;21(2):75\u201388. https:\/\/doi.org\/10.1038\/s41569-023-00924-9.","journal-title":"Nat Rev Cardiol"},{"issue":"3","key":"829_CR2","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","volume":"14","author":"MD Sweeney","year":"2018","unstructured":"Sweeney MD, Sagare AP, Zlokovic BV. Blood\u2013brain barrier breakdown in alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018;14(3):133\u201350. https:\/\/doi.org\/10.1038\/nrneurol.2017.188.","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"829_CR3","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1146\/annurev-cellbio-100617-062608","volume":"35","author":"UH Langen","year":"2019","unstructured":"Langen UH, Ayloo S, Gu C. Development and cell biology of the blood-brain barrier. Annu Rev Cell Dev Biol. 2019;35(1):591\u2013613. https:\/\/doi.org\/10.1146\/annurev-cellbio-100617-062608.","journal-title":"Annu Rev Cell Dev Biol"},{"key":"829_CR4","doi-asserted-by":"publisher","first-page":"101343","DOI":"10.1016\/j.arr.2021.101343","volume":"68","author":"J Burtscher","year":"2021","unstructured":"Burtscher J, Mallet RT, Burtscher M, Millet GP. Hypoxia and brain aging: neurodegeneration or neuroprotection? Ageing Res Rev. 2021;68:101343. https:\/\/doi.org\/10.1016\/j.arr.2021.101343.","journal-title":"Ageing Res Rev"},{"issue":"4","key":"829_CR5","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s10456-021-09796-4","volume":"24","author":"CC Tsao","year":"2021","unstructured":"Tsao CC, Baumann J, Huang SF, Kindler D, Schroeter A, Kachappilly N, et al. Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome. Angiogenesis. 2021;24(4):823\u201342. https:\/\/doi.org\/10.1007\/s10456-021-09796-4.","journal-title":"Angiogenesis"},{"issue":"1\u20132","key":"829_CR6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/03602532.2023.2180028","volume":"55","author":"GQ Liu","year":"2023","unstructured":"Liu GQ, Bai X, Yang JX, Duan YB, Zhu JB, Xiangyang L. Relationship between blood\u2013brain barrier changes and drug metabolism under high-altitude hypoxia: obstacle or opportunity for drug transport? Drug Metab Rev. 2023;55(1\u20132):107\u201325. https:\/\/doi.org\/10.1080\/03602532.2023.2180028.","journal-title":"Drug Metab Rev"},{"issue":"6","key":"829_CR7","doi-asserted-by":"publisher","first-page":"416","DOI":"10.2174\/0113892002318723240802100729","volume":"25","author":"L Tian","year":"2024","unstructured":"Tian L, Liu GQ, Han JJ, Li XY. Effects of high-altitude hypoxia on drug metabolism and pharmacokinetics of sedative-hypnotic drugs and regulatory mechanism. CDM. 2024;25(6):416\u201324. https:\/\/doi.org\/10.2174\/0113892002318723240802100729.","journal-title":"CDM"},{"key":"829_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.addr.2019.11.009","volume":"165-166","author":"R Pandit","year":"2020","unstructured":"Pandit R, Chen L, G\u00f6tz J. The blood-brain barrier: physiology and strategies for drug delivery. Adv Drug Deliv Rev. 2020;165-166:1\u201314. https:\/\/doi.org\/10.1016\/j.addr.2019.11.009.","journal-title":"Adv Drug Deliv Rev"},{"issue":"5","key":"829_CR9","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1124\/pharmrev.120.000025","volume":"75","author":"JA Schulz","year":"2023","unstructured":"Schulz JA, Hartz AMS, Bauer B. ABCB1 and ABCG2 regulation at the blood-brain barrier: potential new targets to improve brain drug delivery. Pharmacol Rev. 2023;75(5):815\u201353. https:\/\/doi.org\/10.1124\/pharmrev.120.000025.","journal-title":"Pharmacol Rev"},{"key":"829_CR10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.pharmthera.2017.10.008","volume":"184","author":"DM McMillan","year":"2018","unstructured":"McMillan DM, Tyndale RF. CYP-mediated drug metabolism in the brain impacts drug response. Pharmacol Ther. 2018;184:189\u2013200. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.10.008.","journal-title":"Pharmacol Ther"},{"issue":"3","key":"829_CR11","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/npp.2010.202","volume":"36","author":"JY Khokhar","year":"2011","unstructured":"Khokhar JY, Tyndale RF. Drug metabolism within the brain changes drug response: selective manipulation of brain CYP2B alters propofol effects. Neuropsychopharmacol. 2011;36(3):692\u2013700. https:\/\/doi.org\/10.1038\/npp.2010.202.","journal-title":"Neuropsychopharmacol"},{"issue":"1\u20132","key":"829_CR12","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1159\/000358128","volume":"93","author":"XY Li","year":"2014","unstructured":"Li XY, Wang XJ, Li YP, Yuan M, Zhu JB, Su XD, et al. Effect of exposure to acute and chronic high-altitude hypoxia on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats. Pharmacology. 2014;93(1\u20132):76\u201383. https:\/\/doi.org\/10.1159\/000358128.","journal-title":"Pharmacology"},{"key":"829_CR13","doi-asserted-by":"publisher","first-page":"574176","DOI":"10.3389\/fphar.2020.574176","volume":"11","author":"YB Duan","year":"2020","unstructured":"Duan YB, Zhu JB, Yang JX, Liu GQ, Bai X, Qu N, et al. Regulation of high-altitude hypoxia on the transcription of CYP450 and UGT1A1 mediated by PXR and CAR. Front Pharmacol. 2020;11:574176. https:\/\/doi.org\/10.3389\/fphar.2020.574176.","journal-title":"Front Pharmacol"},{"issue":"1","key":"829_CR14","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41467-022-35740-1","volume":"14","author":"RH Lou","year":"2023","unstructured":"Lou RH, Cao Y, Li SS, Lang XY, Li YX, Zhang YY, et al. Benchmarking commonly used software suites and analysis workflows for DIA proteomics and phosphoproteomics. Nat Commun. 2023;14(1):94. https:\/\/doi.org\/10.1038\/s41467-022-35740-1.","journal-title":"Nat Commun"},{"issue":"1","key":"829_CR15","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.bcp.2015.08.102","volume":"98","author":"F Hua","year":"2015","unstructured":"Hua F, Shi MJ, Zhu XL, Li M, Wang HX, Yu XM, et al. Transport and uptake of clausenamide enantiomers in CYP3A4-transfected Caco-2 cells: an insight into the efflux-metabolism alliance. Biochemical Pharmacol. 2015;98(1):224\u201330. https:\/\/doi.org\/10.1016\/j.bcp.2015.08.102.","journal-title":"Biochemical Pharmacol"},{"issue":"1","key":"829_CR16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s40478-020-01051-z","volume":"8","author":"SK Halder","year":"2020","unstructured":"Halder SK, Milner R. Mild hypoxia triggers transient blood\u2013brain barrier disruption: a fundamental protective role for microglia. Acta Neuropathol Commun. 2020;8(1):175. https:\/\/doi.org\/10.1186\/s40478-020-01051-z.","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"829_CR17","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.3390\/ph15101303","volume":"15","author":"JB Zhu","year":"2022","unstructured":"Zhu JB, Duan YB, Duo DL, Yang JX, Bai X, Liu GQ, et al. High-altitude hypoxia influences the activities of the drug-metabolizing enzyme CYP3A1 and the pharmacokinetics of four cardiovascular system drugs. Pharmaceuticals (Basel). 2022;15(10):1303. https:\/\/doi.org\/10.3390\/ph15101303.","journal-title":"Pharmaceuticals (Basel)"},{"issue":"5","key":"829_CR18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1208\/s12248-024-00957-z","volume":"26","author":"GQ Liu","year":"2024","unstructured":"Liu GQ, Wang Q, Tian L, Wang MY, Duo DL, Duan YB, et al. Blood\u2013brain barrier permeability is affected by changes in tight junction protein expression at high-altitude hypoxic conditions\u2014this may have implications for brain drug transport. Aaps J. 2024;26(5):90. https:\/\/doi.org\/10.1208\/s12248-024-00957-z.","journal-title":"Aaps J"},{"issue":"4","key":"829_CR19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nrd.2015.21","volume":"15","author":"WA Banks","year":"2016","unstructured":"Banks WA. From blood\u2013brain barrier to blood\u2013brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15(4):275\u201392. https:\/\/doi.org\/10.1038\/nrd.2015.21.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"829_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12987-021-00297-6","volume":"19","author":"B Ozg\u00fcr","year":"2022","unstructured":"Ozg\u00fcr B, Helms HCC, Tornabene E, Brodin B. Hypoxia increases expression of selected blood\u2013brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers. Fluids Barriers CNS. 2022;19(1):1\u201317. https:\/\/doi.org\/10.1186\/s12987-021-00297-6.","journal-title":"Fluids Barriers CNS"},{"key":"829_CR21","doi-asserted-by":"publisher","unstructured":"Cooper E, Woolf Z, Swanson MEV, Correia J, Schweder P, Mee E, et al. Single-cell image analysis reveals over-expression of organic anion transporting polypeptides (OATPs) in human glioblastoma tissue. Neuro-Oncol Adv. 2022;4(1). https:\/\/doi.org\/10.1093\/noajnl\/vdac166.","DOI":"10.1093\/noajnl\/vdac166"},{"key":"829_CR22","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.33594\/000000311","volume":"54","author":"C Zolotoff","year":"2020","unstructured":"Zolotoff C, Voirin AC, Puech C, Roche F, Perek N. Intermittent hypoxia and its impact on Nrf2\/HIF-1\u03b1 expression and ABC transporters: an in vitro human blood-brain barrier model study. Cell Physiol Biochem. 2020;54:1231\u201348.","journal-title":"Cell Physiol Biochem"},{"issue":"4","key":"829_CR23","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1067\/mcp.2002.121789","volume":"71","author":"G J\u00fcrgens","year":"2002","unstructured":"J\u00fcrgens G, Christensen HR, Br\u00f8sen K, Sonne J, Loft S, Olsen NV. Acute hypoxia and cytochrome P450\u2013mediated hepatic drug metabolism in humans. Clin Pharma Ther. 2002;71(4):214\u201320. https:\/\/doi.org\/10.1067\/mcp.2002.121789.","journal-title":"Clin Pharma Ther"},{"issue":"1","key":"829_CR24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1124\/dmd.120.000124","volume":"49","author":"H Takano","year":"2021","unstructured":"Takano H, Yamaguchi JI, Kato S, Hamada M, Tada M, Endo H. Downregulation of CYP1A2, CYP2B6, and CYP3A4 in human hepatocytes by prolyl hydroxylase Domain 2 inhibitors via hypoxia-inducible factor-\u03b1 stabilization. Drug Metab Dispos. 2021;49(1):20\u201330. https:\/\/doi.org\/10.1124\/dmd.120.000124.","journal-title":"Drug Metab Dispos"},{"issue":"2","key":"829_CR25","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.apsb.2022.09.016","volume":"13","author":"Z Mi","year":"2023","unstructured":"Mi Z, Yao Q, Qi Y, Zheng JH, Liu JH, Liu ZG, et al. Salmonella-mediated blood\u2012brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo\/bacterial glioma therapy. Acta Pharmaceutica Sin. B. 2023;13(2):819\u201333. https:\/\/doi.org\/10.1016\/j.apsb.2022.09.016.","journal-title":"Acta Pharmaceutica Sin. B"},{"key":"829_CR26","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.jconrel.2021.05.046","volume":"335","author":"N Pathan","year":"2021","unstructured":"Pathan N, Shende P. Tailoring of P-glycoprotein for effective transportation of actives across blood-brain-barrier. J Control Release. 2021;335:398\u2013407. https:\/\/doi.org\/10.1016\/j.jconrel.2021.05.046.","journal-title":"J Control Release"},{"issue":"5","key":"829_CR27","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.apsb.2016.07.016","volume":"6","author":"WD Hedrich","year":"2016","unstructured":"Hedrich WD, Hassan HE, Wang H. Insights into CYP2B6-mediated drug\u2013drug interactions. Acta Pharmaceutica Sin. B. 2016;6(5):413\u201325. https:\/\/doi.org\/10.1016\/j.apsb.2016.07.016.","journal-title":"Acta Pharmaceutica Sin. B"},{"issue":"23","key":"829_CR28","doi-asserted-by":"publisher","first-page":"14667","DOI":"10.3390\/ijms232314667","volume":"23","author":"AB Chai","year":"2022","unstructured":"Chai AB, Callaghan R, Gelissen IC. Regulation of p-glycoprotein in the brain. IJMS. 2022;23(23):14667. https:\/\/doi.org\/10.3390\/ijms232314667.","journal-title":"IJMS"},{"issue":"1","key":"829_CR29","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/cpt.892","volume":"104","author":"KS Burgess","year":"2018","unstructured":"Burgess KS, Ipe J, Swart M, Metzger IF, Lu J, Gufford BT, et al. Variants in the CYP2B6 3\u2032UTR alter in vitro and in vivo CYP2B6 activity: potential role of MicroRNAs. Clin Pharma Ther. 2018;104(1):130\u201338. https:\/\/doi.org\/10.1002\/cpt.892.","journal-title":"Clin Pharma Ther"},{"issue":"2","key":"829_CR30","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1124\/dmd.121.000681","volume":"50","author":"YB Duan","year":"2022","unstructured":"Duan YB, Bai X, Yang JX, Zhou Y, Gu WQ, Liu GQ, et al. Exposure to high-altitude environment is associated with drug transporters change: microRNA-873-5p-mediated alteration of function and expression levels of drug transporters under hypoxia. Drug Metab Dispos. 2022;50(2):174\u201386. https:\/\/doi.org\/10.1124\/dmd.121.000681.","journal-title":"Drug Metab Dispos"},{"key":"829_CR31","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.jconrel.2022.08.051","volume":"350","author":"B Sethi","year":"2022","unstructured":"Sethi B, Kumar V, Mahato K, Coulter DW, Mahato RI. Recent advances in drug delivery and targeting to the brain. J Control Release. 2022;350:668\u201387. https:\/\/doi.org\/10.1016\/j.jconrel.2022.08.051.","journal-title":"J Control Release"},{"issue":"3","key":"829_CR32","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.apsb.2015.03.012","volume":"5","author":"Y Chen","year":"2015","unstructured":"Chen Y, Yan Q, Zhong M, Zhao Q, Liu J, Di D, et al. Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method. Acta Pharmaceutica Sin. B. 2015;5(3):238\u201345. https:\/\/doi.org\/10.1016\/j.apsb.2015.03.012.","journal-title":"Acta Pharmaceutica Sin. B"},{"issue":"4","key":"829_CR33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1592\/phco.29.4.365","volume":"29","author":"JM Dopp","year":"2009","unstructured":"Dopp JM, Moran JJ, Abel NJ, Wiegert NA, Cowgill JB, Olson EB, et al. Influence of intermittent hypoxia on myocardial and hepatic P-glycoprotein expression in a rodent model. Pharmacotherapy. 2009;29(4):365\u201372. https:\/\/doi.org\/10.1592\/phco.29.4.365.","journal-title":"Pharmacotherapy"},{"issue":"6","key":"829_CR34","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/sj.bjp.0705543","volume":"140","author":"C Fradette","year":"2003","unstructured":"Fradette C, du Souich P. Hypoxia-inducible factor-1 and activator protein-1 modulate the upregulation of CYP3A6 induced by hypoxia. Br J Pharmacol. 2003;140(6):1146\u201354. https:\/\/doi.org\/10.1038\/sj.bjp.0705543.","journal-title":"Br J Pharmacol"},{"issue":"11","key":"829_CR35","doi-asserted-by":"publisher","first-page":"960","DOI":"10.2174\/1389200219666180529112913","volume":"19","author":"XJ Zhou","year":"2018","unstructured":"Zhou XJ, Nian YQ, Qiao YJ, Yang M, Xin YY, Li XY. Hypoxia plays a key role in the pharmacokinetic changes of drugs at high altitude. CDM. 2018;19(11):960\u201369. https:\/\/doi.org\/10.2174\/1389200219666180529112913.","journal-title":"CDM"},{"issue":"4","key":"829_CR36","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1089\/ham.2014.1026","volume":"15","author":"XY Li","year":"2014","unstructured":"Li XY, Wang XJ, Li YP, Zhu JB, Su XD, Yao XC, et al. The activity, protein, and mRNA expression of CYP2E1 and CYP3A1 in rats after exposure to acute and chronic high altitude hypoxia. High Alt Med Biol. 2014;15(4):491\u201396. https:\/\/doi.org\/10.1089\/ham.2014.1026.","journal-title":"High Alt Med Biol"}],"container-title":["Fluids and Barriers of the CNS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12987-026-00829-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12987-026-00829-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12987-026-00829-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:03:17Z","timestamp":1787580197000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12987-026-00829-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["829"],"URL":"https:\/\/doi.org\/10.1186\/s12987-026-00829-y","relation":{},"ISSN":["2045-8118"],"issn-type":[{"value":"2045-8118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"assertion":[{"value":"28 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the Animal Ethics Committee of Qinghai University (Permit NO. 2022\u201324). All experimental procedure were performed following the guidelines of the Ethics Committee for Animal Experiments.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"100"}}