{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T09:50:19Z","timestamp":1787478619202,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several sleep-related breathing disorders provoke repeated hypoxia stresses, which potentially lead to neurological diseases, such as cognitive impairment. Nevertheless, consequences of repeated intermittent hypoxia on the blood-brain barrier (BBB) are less recognized. This study compared two methods of intermittent hypoxia induction on the cerebral endothelium of the BBB: one using hydralazine and the other using a hypoxia chamber. These cycles were performed on an endothelial cell and astrocyte coculture model. Na-Fl permeability, tight junction protein, and ABC transporters (P-gp and MRP-1) content were evaluated with or without HIF-1 inhibitors YC-1. Our results demonstrated that hydralazine as well as intermittent physical hypoxia progressively altered BBB integrity, as shown by an increase in Na-Fl permeability. This alteration was accompanied by a decrease in concentration of tight junction proteins ZO-1 and claudin-5. In turn, microvascular endothelial cells up-regulated the expression of P-gp and MRP-1. An alteration was also found under hydralazine after the third cycle. On the other hand, the third intermittent hypoxia exposure showed a preservation of BBB characteristics. Furthermore, inhibition of HIF-1\u03b1 with YC-1 prevented BBB dysfunction after hydralazine treatment. In the case of physical intermittent hypoxia, we observed an incomplete reversion suggesting that other biological mechanisms may be involved in BBB dysfunction. In conclusion, intermittent hypoxia led to an alteration of the BBB model with an adaptation observed after the third cycle.<\/jats:p>","DOI":"10.3390\/ijms24055062","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T02:07:38Z","timestamp":1678154858000},"page":"5062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Loss of Blood-Brain Barrier Integrity in an In Vitro Model Subjected to Intermittent Hypoxia: Is Reversion Possible with a HIF-1\u03b1 Pathway Inhibitor?"],"prefix":"10.3390","volume":"24","author":[{"given":"Anne Clo\u00e9","family":"Voirin","sequence":"first","affiliation":[{"name":"INSERM, SAINBIOSE U1059, Univ. Jean Monnet Saint-\u00c9tienne, Mines Saint Etienne, F-42023 Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Chatard","sequence":"additional","affiliation":[{"name":"INSERM, SAINBIOSE U1059, Univ. Jean Monnet Saint-\u00c9tienne, Mines Saint Etienne, F-42023 Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-300X","authenticated-orcid":false,"given":"Anne","family":"Brian\u00e7on-Marjollet","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2 Laboratory U1300, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-2358","authenticated-orcid":false,"given":"Jean Louis","family":"Pepin","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2 Laboratory U1300, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Perek","sequence":"additional","affiliation":[{"name":"INSERM, SAINBIOSE U1059, Univ. Jean Monnet Saint-\u00c9tienne, Mines Saint Etienne, F-42023 Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-7958","authenticated-orcid":false,"given":"Frederic","family":"Roche","sequence":"additional","affiliation":[{"name":"INSERM, SAINBIOSE U1059, Univ. Jean Monnet Saint-\u00c9tienne, Mines Saint Etienne, F-42023 Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/ham.2012.1052","article-title":"HIF-1 at the Blood-Brain Barrier: A Mediator of Permeability?","volume":"13","author":"Ogunshola","year":"2012","journal-title":"High Alt. Med. Biol."},{"key":"ref_2","first-page":"w13892","article-title":"Breaking and Building the Wall: The Biology of the Blood-Brain Barrier in Health and Disease","volume":"143","author":"Keller","year":"2013","journal-title":"Swiss Med. Wkly."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1528-1167.2012.03696.x","article-title":"Overview and Introduction: The Blood-Brain Barrier in Health and Disease","volume":"53","author":"Abbott","year":"2012","journal-title":"Epilepsia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, Maintenance and Disruption of the Blood-Brain Barrier","volume":"19","author":"Obermeier","year":"2013","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/jcbfm.2010.148","article-title":"Astrocytes and Pericytes Differentially Modulate Blood-Brain Barrier Characteristics during Development and Hypoxic Insult","volume":"31","author":"Taboada","year":"2011","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1046\/j.1471-4159.2002.01186.x","article-title":"Intercommunications between Brain Capillary Endothelial Cells and Glial Cells Increase the Transcellular Permeability of the Blood-Brain Barrier during Ischaemia","volume":"83","author":"Brillault","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.regpep.2004.05.023","article-title":"Effects of Hypoxia on Endothelial\/Pericytic Co-Culture Model of the Blood-Brain Barrier","volume":"123","author":"Hayashi","year":"2004","journal-title":"Regul. Pept."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1208\/s12248-017-0076-6","article-title":"Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System","volume":"19","author":"Lochhead","year":"2017","journal-title":"AAPS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/jgs.13321","article-title":"Associations between Sleep-Disordered Breathing, Nocturnal Hypoxemia, and Subsequent Cognitive Decline in Older Community-Dwelling Men: The Osteoporotic Fractures in Men Sleep Study","volume":"63","author":"Blackwell","year":"2015","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jagp.2016.11.009","article-title":"Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study","volume":"25","author":"Kerner","year":"2017","journal-title":"Am. J. Geriatr. Psychiatry Off. J. Am. Assoc. Geriatr. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/sleep\/33.4.515","article-title":"Cognitive Function and Sleep Related Breathing Disorders in a Healthy Elderly Population: The SYNAPSE Study","volume":"33","author":"Sforza","year":"2010","journal-title":"Sleep"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/jon.12288","article-title":"Water Exchange across the Blood-Brain Barrier in Obstructive Sleep Apnea: An MRI Diffusion-Weighted Pseudo-Continuous Arterial Spin Labeling Study","volume":"25","author":"Palomares","year":"2015","journal-title":"J. Neuroimaging Off. J. Am. Soc. Neuroimaging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S2213-2600(15)00090-9","article-title":"Sleep Apnoea and the Brain: A Complex Relationship","volume":"3","author":"Rosenzweig","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.jagp.2016.01.134","article-title":"Obstructive Sleep Apnea Is Linked to Depression and Cognitive Impairment: Evidence and Potential Mechanisms","volume":"24","author":"Kerner","year":"2016","journal-title":"Am. J. Geriatr. Psychiatry Off. J. Am. Assoc. Geriatr. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.resp.2012.10.012","article-title":"Altered Aquaporins in the Brains of Mice Submitted to Intermittent Hypoxia Model of Sleep Apnea","volume":"185","author":"Baronio","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.smrv.2011.01.003","article-title":"A Systematic Review of CPAP Adherence across Age Groups: Clinical and Empiric Insights for Developing CPAP Adherence Interventions","volume":"15","author":"Sawyer","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"ref_17","first-page":"145","article-title":"Cognitive Function and Depressivity before and after Cpap Treatment in Obstructive Sleep Apnea Patients","volume":"38","author":"Hobzova","year":"2017","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/jgs.15758","article-title":"CPAP Adherence May Slow 1-Year Cognitive Decline in Older Adults with Mild Cognitive Impairment and Apnea","volume":"67","author":"Richards","year":"2019","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.smrv.2012.12.003","article-title":"Obstructive Sleep Apnea and Cognitive Impairment: Addressing the Blood-Brain Barrier","volume":"18","author":"Lim","year":"2014","journal-title":"Sleep Med. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/jcp.24544","article-title":"Hypoxia Selectively Disrupts Brain Microvascular Endothelial Tight Junction Complexes through a Hypoxia-Inducible Factor-1 (HIF-1) Dependent Mechanism","volume":"229","author":"Engelhardt","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physiol.00045.2008","article-title":"Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1","volume":"24","author":"Semenza","year":"2009","journal-title":"Physiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"159","DOI":"10.5114\/fn.2018.78693","article-title":"The Impact of Chronic Intermittent Hypoxia on the Expression of Intercellular Cell Adhesion Molecule-1 and Vascular Endothelial Growth Factor in the Ischemia-Reperfusion Rat Model","volume":"56","author":"Yang","year":"2018","journal-title":"Folia Neuropathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1152\/physrev.00030.2011","article-title":"Adaptive and Maladaptive Cardiorespiratory Responses to Continuous and Intermittent Hypoxia Mediated by Hypoxia-Inducible Factors 1 and 2","volume":"92","author":"Prabhakar","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-physiol-021113-170322","article-title":"Hypoxia-Inducible Factor 1 and Cardiovascular Disease","volume":"76","author":"Semenza","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.resp.2008.07.006","article-title":"Transcriptional Responses to Intermittent Hypoxia","volume":"164","author":"Nanduri","year":"2008","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-med-042915-102623","article-title":"Obstructive Sleep Apnea: Update and Future","volume":"68","author":"Lim","year":"2017","journal-title":"Annu. Rev. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1159\/000479399","article-title":"Hydralazine Is a Suitable Mimetic Agent of Hypoxia to Study the Impact of Hypoxic Stress on In Vitro Blood-Brain Barrier Model","volume":"42","author":"Chatard","year":"2017","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chatard, M., Puech, C., Roche, F., and Perek, N. (2016). Hypoxic Stress Induced by Hydralazine Leads to a Loss of Blood-Brain Barrier Integrity and an Increase in Efflux Transporter Activity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158010"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.RES.0000134924.89412.70","article-title":"Novel Mechanism of Action for Hydralazine: Induction of Hypoxia-Inducible Factor-1alpha, Vascular Endothelial Growth Factor, and Angiogenesis by Inhibition of Prolyl Hydroxylases","volume":"95","author":"Knowles","year":"2004","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1139\/bcb-2019-0117","article-title":"Protective Effect of Hydralazine on a Cellular Model of Parkinson\u2019s Disease: A Possible Role of Hypoxia-Inducible Factor (HIF)-1\u03b1","volume":"98","author":"Mehrabani","year":"2020","journal-title":"Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.neuroscience.2015.07.051","article-title":"Minocycline Ameliorates Hypoxia-Induced Blood-Brain Barrier Damage by Inhibition of HIF-1\u03b1 through SIRT-3\/PHD-2 Degradation Pathway","volume":"304","author":"Yang","year":"2015","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C460","DOI":"10.1152\/ajpcell.00098.2017","article-title":"An Innovative Intermittent Hypoxia Model for Cell Cultures Allowing Fast Po(2) Oscillations with Minimal Gas Consumption","volume":"313","author":"Minoves","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ijpharm.2018.09.040","article-title":"Assessment of HBEC-5i Endothelial Cell Line Cultivated in Astrocyte Conditioned Medium as a Human Blood-Brain Barrier Model for ABC Drug Transport Studies","volume":"551","author":"Puech","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1113\/EP086051","article-title":"Impact of Obstructive Sleep Apnoea and Intermittent Hypoxia on Cardiovascular and Cerebrovascular Regulation","volume":"102","author":"Beaudin","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1440-1843.2012.02255.x","article-title":"Neurocognitive Function in Obstructive Sleep Apnoea: A Meta-Review","volume":"18","author":"Bucks","year":"2013","journal-title":"Respirology"},{"key":"ref_36","first-page":"2260","article-title":"The Effect of 3-(5\u2019-Hydroxymethyl-2\u2019-Furyl)-1-Benzylindazole (YC-1) on Cell Viability under Hypoxia","volume":"19","author":"Tsui","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yan, J., Zhou, B., Taheri, S., and Shi, H. (2011). Differential Effects of HIF-1 Inhibition by YC-1 on the Overall Outcome and Blood-Brain Barrier Damage in a Rat Model of Ischemic Stroke. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027798"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s00432-010-0828-5","article-title":"Expression and Significance of Hypoxia-Inducible Factor-1 Alpha and MDR1\/P-Glycoprotein in Human Colon Carcinoma Tissue and Cells","volume":"136","author":"Ding","year":"2010","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1124\/mol.107.036418","article-title":"Inhibition of Hypoxia-Induced Increase of Blood-Brain Barrier Permeability by YC-1 through the Antagonism of HIF-1alpha Accumulation and VEGF Expression","volume":"72","author":"Yeh","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Won, S., Sayeed, I., Peterson, B.L., Wali, B., Kahn, J.S., and Stein, D.G. (2015). Vitamin D Prevents Hypoxia\/Reoxygenation-Induced Blood-Brain Barrier Disruption via Vitamin D Receptor-Mediated NF-KB Signaling Pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122821"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00221-011-2702-3","article-title":"Effects of Hyperbaric Oxygen on the Expression of Claudins after Cerebral Ischemia-Reperfusion in Rats","volume":"212","author":"Zhao","year":"2011","journal-title":"Exp. Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H1485","DOI":"10.1152\/ajpheart.00645.2001","article-title":"Cerebral Microvascular Changes in Permeability and Tight Junctions Induced by Hypoxia-Reoxygenation","volume":"282","author":"Mark","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1592\/phco.29.4.365","article-title":"Influence of Intermittent Hypoxia on Myocardial and Hepatic P-Glycoprotein Expression in a Rodent Model","volume":"29","author":"Dopp","year":"2009","journal-title":"Pharmacotherapy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.neulet.2007.12.017","article-title":"Repetitive\/Temporal Hypoxia Increased P-Glycoprotein Expression in Cultured Rat Brain Microvascular Endothelial Cells in Vitro","volume":"432","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1471-4159.2009.06306.x","article-title":"P-Glycoprotein Expression in Immortalised Rat Brain Endothelial Cells: Comparisons Following Exogenously Applied Hydrogen Peroxide and after Hypoxia-Reoxygenation","volume":"111","author":"Robertson","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12987-017-0055-4","article-title":"Nrf2 Signaling Increases Expression of ATP-Binding Cassette Subfamily C MRNA Transcripts at the Blood-Brain Barrier Following Hypoxia-Reoxygenation Stress","volume":"14","author":"Ibbotson","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.33594\/000000311","article-title":"Intermittent Hypoxia and Its Impact on Nrf2\/HIF-1\u03b1 Expression and ABC Transporters: An in Vitro Human Blood-Brain Barrier Model Study","volume":"54","author":"Zolotoff","year":"2020","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.freeradbiomed.2009.07.035","article-title":"Nrf2:INrf2 (Keap1) Signaling in Oxidative Stress","volume":"47","author":"Kaspar","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"146647","DOI":"10.1016\/j.brainres.2020.146647","article-title":"Inflammatory Stress Induced by a Combination of Cytokines (IL-6, IL-17, TNF-\u03b1) Leads to a Loss of Integrity on BEnd.3 Endothelial Cells in Vitro BBB Model","volume":"1730","author":"Voirin","year":"2020","journal-title":"Brain Res."},{"key":"ref_50","first-page":"1003","article-title":"Serum Inflammatory Markers in Obstructive Sleep Apnea: A Meta-Analysis","volume":"9","author":"Nadeem","year":"2013","journal-title":"J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11309","DOI":"10.1038\/s41598-020-68374-8","article-title":"Sera of Elderly Obstructive Sleep Apnea Patients Alter Blood-Brain Barrier Integrity in Vitro: A Pilot Study","volume":"10","author":"Voirin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12305","DOI":"10.1038\/s41598-022-15592-x","article-title":"Effects of Intermittent Hypoxia with Thrombin in an in Vitro Model of Human Brain Endothelial Cells and Their Impact on PAR-1\/PAR-3 Cleavage","volume":"12","author":"Zolotoff","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.0808698106","article-title":"VEGF-Mediated Disruption of Endothelial CLN-5 Promotes Blood-Brain Barrier Breakdown","volume":"106","author":"Argaw","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2018.07.021","article-title":"Astrocyte Activation and Reactive Gliosis\u2014A New Target in Stroke?","volume":"689","author":"Pekny","year":"2019","journal-title":"Neurosci. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/5062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:49:21Z","timestamp":1760122161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/5062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24055062"],"URL":"https:\/\/doi.org\/10.3390\/ijms24055062","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]}}}