{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:54:09Z","timestamp":1787662449423,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad de las Am\u00e9ricas (UDLA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stroke is a leading global cause of mortality and long-term disability, with cerebral edema constituting a major contributor to early neurological deterioration and poor outcomes. Aquaporin-4 (AQP4), the predominant water channel in the central nervous system, plays a paradoxical role in stroke-related brain edema, facilitating both the formation and clearance of excess fluid depending on the pathological context. This review explores the biphasic function of AQP4 across cytotoxic and vasogenic edema, emphasizing its dynamic regulation, subcellular localization, and implications for therapeutic intervention. Evidence from rodent models shows that AQP4 exacerbates cytotoxic edema in acute ischemia by promoting intracellular water influx into astrocytes, whereas in vasogenic edema, it supports fluid reabsorption and glymphatic clearance, thereby alleviating brain swelling. Human studies corroborate AQP4 upregulation in infarcted regions and suggest a potential role for AQP4 polymorphisms and circulating levels as biomarkers of stroke severity and outcome, although larger cohorts and more robust methodological designs are needed. This review also discusses emerging pharmacological strategies to modulate AQP4 activity, including inhibitors, trafficking modulators, and gene-targeted delivery systems, while highlighting challenges in achieving phase-specific modulation. Given its central role in both injury and recovery, AQP4 emerges as a promising yet complex therapeutic target for personalized management of stroke-induced brain edema. Future directions include real-time imaging of AQP4 function, genotype-stratified clinical trials, and integration of AQP4 modulation with current stroke treatment protocols.<\/jats:p>","DOI":"10.3390\/ijms26178178","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:10:36Z","timestamp":1756080636000},"page":"8178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Aquaporin-4 in Stroke and Brain Edema\u2014Friend or Foe?"],"prefix":"10.3390","volume":"26","author":[{"given":"Cecilia Alejandra","family":"Garc\u00eda R\u00edos","sequence":"first","affiliation":[{"name":"Carrera de Medicina, Facultad Ciencias de la Salud, Universidad Nacional de Chimborazo (UNACH), Riobamba 060108, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-6460","authenticated-orcid":false,"given":"Jose E.","family":"Leon-Rojas","sequence":"additional","affiliation":[{"name":"Cerebro, Emoci\u00f3n y Conducta (CEC) Research Group, Escuela de Medicina, Universidad de las Am\u00e9ricas (UDLA), Quito 170124, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","unstructured":"(2025, May 25). WHO EMRO|Stroke, Cerebrovascular Accident|Health Topics. Available online: http:\/\/www.emro.who.int\/health-topics\/stroke-cerebrovascular-accident\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e036142","DOI":"10.1161\/JAHA.124.036142","article-title":"Projections of the Stroke Burden at the Global, Regional, and National Levels up to 2050 Based on the Global Burden of Disease Study 2021","volume":"13","author":"Cheng","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gu, Y., Zhou, C., Piao, Z., Yuan, H., Jiang, H., Wei, H., Zhou, Y., Nan, G., and Ji, X. (2022). Cerebral Edema after Ischemic Stroke: Pathophysiology and Underlying Mechanisms. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.988283"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"DeHoff, G., and Lau, W. (2022). Medical Management of Cerebral Edema in Large Hemispheric Infarcts. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.857640"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1007\/s00467-006-0411-0","article-title":"Aquaporin-4 and Brain Edema","volume":"22","author":"Papadopoulos","year":"2007","journal-title":"Pediatr. Nephrol. Berl. Ger."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1096\/fj.04-1723fje","article-title":"Aquaporin-4 Facilitates Reabsorption of Excess Fluid in Vasogenic Brain Edema","volume":"18","author":"Papadopoulos","year":"2004","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/72256","article-title":"Aquaporin-4 Deletion in Mice Reduces Brain Edema after Acute Water Intoxication and Ischemic Stroke","volume":"6","author":"Manley","year":"2000","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1152\/physrev.00011.2013","article-title":"Physiological Roles of Aquaporin-4 in Brain","volume":"93","author":"Nagelhus","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nrn1252","article-title":"The Molecular Basis of Water Transport in the Brain","volume":"4","author":"Ottersen","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","first-page":"4405","article-title":"Super-Resolution Imaging of Aquaporin-4 Orthogonal Arrays of Particles in Cell Membranes","volume":"125","author":"Rossi","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tins.2020.04.003","article-title":"The Brain\u2019s Glymphatic System: Current Controversies","volume":"43","author":"Mestre","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The Glymphatic Pathway in Neurological Disorders","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15280","DOI":"10.1074\/jbc.M801425200","article-title":"Glial Cell Aquaporin-4 Overexpression in Transgenic Mice Accelerates Cytotoxic Brain Swelling","volume":"283","author":"Yang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1755-5949.2012.00308.x","article-title":"AQP4 Knockout Aggravates Ischemia\/Reperfusion Injury in Mice","volume":"18","author":"Zeng","year":"2012","journal-title":"CNS Neurosci. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1471-4159.2005.03362.x","article-title":"Aquaporin-4 Gene Deletion in Mice Increases Focal Edema Associated with Staphylococcal Brain Abscess","volume":"95","author":"Bloch","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1002\/jnr.20819","article-title":"Time Course of Aquaporin Expression after Transient Focal Cerebral Ischemia in Mice","volume":"83","author":"Ribeiro","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Filippidis, A.S., Carozza, R.B., and Rekate, H.L. (2016). Aquaporins in Brain Edema and Neuropathological Conditions. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010055"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sun, C., Lin, L., Yin, L., Hao, X., Tian, J., Zhang, X., Ren, Y., Li, C., and Yang, Y. (2022). Acutely Inhibiting AQP4 With TGN-020 Improves Functional Outcome by Attenuating Edema and Peri-Infarct Astrogliosis After Cerebral Ischemia. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.870029"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lee, A.-H., Tai, S.-H., Huang, S.-Y., Chang, L.-D., Chen, L.-Y., Chen, Y.-N., Hsu, H.-H., and Lee, E.-J. (2024). Melatonin Improves Vasogenic Edema via Inhibition to Water Channel Aquaporin-4 (AQP4) and Metalloproteinase-9 (MMP-9) Following Permanent Focal Cerebral Ischemia. Biomedicines, 12.","DOI":"10.3390\/biomedicines12102184"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10072-010-0431-1","article-title":"Pretreatment with a Novel Aquaporin 4 Inhibitor, TGN-020, Significantly Reduces Ischemic Cerebral Edema","volume":"32","author":"Igarashi","year":"2011","journal-title":"Neurol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12987-024-00527-7","article-title":"Role of Aquaporin-4 Polarization in Extracellular Solute Clearance","volume":"21","author":"Bojarskaite","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17815","DOI":"10.1073\/pnas.1110655108","article-title":"Glial-Conditional Deletion of Aquaporin-4 (Aqp4) Reduces Blood-Brain Water Uptake and Confers Barrier Function on Perivascular Astrocyte Endfeet","volume":"108","author":"Vindedal","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Krishnan, K., Campos, P.B., Nguyen, T.N., Tan, C.W., Chan, S.L., Appleton, J.P., Law, Z., Hollingworth, M., Kirkman, M.A., and England, T.J. (2023). Cerebral Edema in Intracerebral Hemorrhage: Pathogenesis, Natural History, and Potential Treatments from Translation to Clinical Trials. Front. Stroke, 2.","DOI":"10.3389\/fstro.2023.1256664"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chu, H., Tang, Y., and Dong, Q. (2013). Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066051"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/labinvest.2014.84","article-title":"Erythropoietin Protects against Hemorrhagic Blood\u2013Brain Barrier Disruption through the Effects of Aquaporin-4","volume":"94","author":"Chu","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_27","unstructured":"Martin, R.D., Boling, W., Chen, G., and Zhang, J.H. (2020). Aquaporin4 Knockout Aggravates Early Brain Injury Following Subarachnoid Hemorrhage Through Impairment of the Glymphatic System in Rat Brain. Subarachnoid Hemorrhage: Neurological Care and Protection, Springer International Publishing."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, E., Peng, X., Ma, H., Zhang, Y., Yang, X., Zhang, Y., Sun, L., and Yan, J. (2021). The Involvement of Aquaporin-4 in the Interstitial Fluid Drainage Impairment Following Subarachnoid Hemorrhage. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.611494"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xiong, A., Li, J., Xiong, R., Xia, Y., Jiang, X., Cao, F., Lu, H., Xu, J., and Shan, F. (2022). Inhibition of HIF-1\u03b1-AQP4 Axis Ameliorates Brain Edema and Neurological Functional Deficits in a Rat Controlled Cortical Injury (CCI) Model. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-06773-9"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.cell.2020.03.037","article-title":"Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema","volume":"181","author":"Kitchen","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Lei, L., Zhou, H., Lu, X., Cai, F., and Li, T. (2022). Roles of Micro Ribonucleic Acids in Astrocytes After Cerebral Stroke. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.890762"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nesverova, V., and T\u00f6rnroth-Horsefield, S. (2019). Phosphorylation-Dependent Regulation of Mammalian Aquaporins. Cells, 8.","DOI":"10.3390\/cells8020082"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.neuro.2019.03.006","article-title":"Involvement of Mitogen-Activated Protein Kinase Pathways in Ferrous Iron-Induced Aquaporin-4 Expression in Cultured Astrocytes","volume":"73","author":"Zhong","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Markou, A., Unger, L., Abir-Awan, M., Saadallah, A., Halsey, A., Balklava, Z., Conner, M., T\u00f6rnroth-Horsefield, S., Greenhill, S.D., and Conner, A. (2022). Molecular Mechanisms Governing Aquaporin Relocalisation. Biochim. Biophys. Acta BBA Biomembr., 1864.","DOI":"10.1016\/j.bbamem.2021.183853"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16873","DOI":"10.1074\/jbc.M115.646034","article-title":"Identification and Molecular Mechanisms of the Rapid Tonicity-Induced Relocalization of the Aquaporin 4 Channel","volume":"290","author":"Kitchen","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainres.2013.09.022","article-title":"The Internalization and Lysosomal Degradation of Brain AQP4 after Ischemic Injury","volume":"1539","author":"Huang","year":"2013","journal-title":"Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/978-3-211-85578-2_84","article-title":"The Modulation of Aquaporin-4 by Using PKC-Activator (Phorbol Myristate Acetate) and V1a Receptor Antagonist (SR49059) Following Middle Cerebral Artery Occlusion\/Reperfusion in the Rat","volume":"102","author":"Okuno","year":"2008","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C1292","DOI":"10.1152\/ajpcell.00561.2003","article-title":"Evidence for Stabilization of Aquaporin-2 Folding Mutants by N-Linked Glycosylation in Endoplasmic Reticulum","volume":"287","author":"Buck","year":"2004","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/brain\/awab311","article-title":"Emerging Roles for Dynamic Aquaporin-4 Subcellular Relocalization in CNS Water Homeostasis","volume":"145","author":"Salman","year":"2022","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yang, J., Cao, C., Liu, J., Liu, Y., Lu, J., Yu, H., Li, X., Wu, J., Yu, Z., and Li, H. (2024). Dystrophin 71 Deficiency Causes Impaired Aquaporin-4 Polarization Contributing to Glymphatic Dysfunction and Brain Edema in Cerebral Ischemia. Neurobiol. Dis., 199.","DOI":"10.1016\/j.nbd.2024.106586"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ishida, H., Vogel, H.J., Conner, A.C., Kitchen, P., Bill, R.M., and MacDonald, J.A. (2022). Simultaneous Binding of the N- and C-Terminal Cytoplasmic Domains of Aquaporin 4 to Calmodulin. Biochim. Biophys. Acta BBA Biomembr., 1864.","DOI":"10.1016\/j.bbamem.2021.183837"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00401-003-0709-y","article-title":"Enhanced Expression of Aquaporin 4 in Human Brain with Infarction","volume":"106","author":"Aoki","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40478-015-0239-6","article-title":"Heterogeneity of Aquaporin-4 Localization and Expression after Focal Cerebral Ischemia Underlies Differences in White versus Grey Matter Swelling","volume":"3","author":"Stokum","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, S., Shao, L., and Ma, L. (2021). Cerebral Edema Formation After Stroke: Emphasis on Blood\u2013Brain Barrier and the Lymphatic Drainage System of the Brain. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.716825"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1161\/STROKEAHA.107.500785","article-title":"The Role of Aquaporin-4 Polymorphisms in the Development of Brain Edema After Middle Cerebral Artery Occlusion","volume":"39","author":"Kleffner","year":"2008","journal-title":"Stroke"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1089\/neu.2014.3347","article-title":"AQP4 Tag Single Nucleotide Polymorphisms in Patients with Traumatic Brain Injury","volume":"31","author":"Dardiotis","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Czy\u017cewski, W., Litak, J., Sobstyl, J., Mandat, T., Torres, K., and Sta\u015bkiewicz, G. (2024). Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126553"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"134580","DOI":"10.1016\/j.neulet.2019.134580","article-title":"Circulating Aquaporin-4 as A Biomarker of Early Neurological Improvement in Stroke Patients: A Pilot Study","volume":"714","author":"Ramiro","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2020.06.007","article-title":"Aquaporin-4 Polymorphisms Predict Amyloid Burden and Clinical Outcome in the Alzheimer\u2019s Disease Spectrum","volume":"97","author":"Chandra","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40035-024-00451-8","article-title":"Aquaporin-4 as a Cerebrospinal Fluid Biomarker of Alzheimer\u2019s Disease","volume":"13","author":"Halbgebauer","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/brain\/awf151","article-title":"A Role for Humoral Mechanisms in the Pathogenesis of Devic\u2019s Neuromyelitis Optica","volume":"125","author":"Lucchinetti","year":"2002","journal-title":"Brain J. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S1474-4422(12)70133-3","article-title":"Aquaporin 4 and Neuromyelitis Optica","volume":"11","author":"Papadopoulos","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/ana.22657","article-title":"Anti-Aquaporin-4 Monoclonal Antibody Blocker Therapy for Neuromyelitis Optica","volume":"71","author":"Tradtrantip","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1056\/NEJMoa1900866","article-title":"Eculizumab in Aquaporin-4\u2013Positive Neuromyelitis Optica Spectrum Disorder","volume":"381","author":"Pittock","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tang, G., and Yang, G.-Y. (2016). Aquaporin-4: A Potential Therapeutic Target for Cerebral Edema. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101413"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1080\/14728222.2017.1398236","article-title":"The Aquaporin-4 Water Channel as a Potential Drug Target in Neurological Disorders","volume":"21","author":"Verkman","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Abir-Awan, M., Kitchen, P., Salman, M.M., Conner, M.T., Conner, A.C., and Bill, R.M. (2019). Inhibitors of Mammalian Aquaporin Water Channels. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071589"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jsb.2008.11.010","article-title":"Acetazolamide Reversibly Inhibits Water Conduction by Aquaporin-4","volume":"166","author":"Tanimura","year":"2009","journal-title":"J. Struct. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/mol.108.053744","article-title":"Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site","volume":"76","author":"Migliati","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_60","first-page":"3090","article-title":"Effects of Dexamethasone on Aquaporin-4 Expression in Brain Tissue of Rat with Bacterial Meningitis","volume":"8","author":"Du","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_61","first-page":"1508","article-title":"Inhibition of Aquaporin-4 Expression in Astrocytes by RNAi Determines Alteration in Cell Morphology, Growth, and Water Transport and Induces Changes in Ischemia-Related Genes","volume":"17","author":"Nicchia","year":"2003","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/glia.24639","article-title":"Aquaporin-4 Activation Facilitates Glymphatic System Function and Hematoma Clearance Post-Intracerebral Hemorrhage","volume":"73","author":"Chen","year":"2025","journal-title":"Glia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"797","DOI":"10.7150\/ijms.82677","article-title":"Trifluoperazine Reduces Apoptosis and Inflammatory Responses in Traumatic Brain Injury by Preventing the Accumulation of Aquaporin4 on the Surface of Brain Cells","volume":"20","author":"Xing","year":"2023","journal-title":"Int. J. Med. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1083\/jcb.200106158","article-title":"In Vivo Requirement of the \u03b1-Syntrophin PDZ Domain for the Sarcolemmal Localization of nNOS and Aquaporin-4","volume":"155","author":"Adams","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_65","first-page":"340","article-title":"An Aquaporin 4 Antisense Oligonucleotide Loaded, Brain Targeted Nanoparticulate System Design","volume":"69","author":"Kozlu","year":"2014","journal-title":"Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1038\/s41467-020-18115-2","article-title":"Circadian Control of Brain Glymphatic and Lymphatic Fluid Flow","volume":"11","author":"Hablitz","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eaav5447","DOI":"10.1126\/sciadv.aav5447","article-title":"Increased Glymphatic Influx Is Correlated with High EEG Delta Power and Low Heart Rate in Mice under Anesthesia","volume":"5","author":"Hablitz","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"196","DOI":"10.13104\/imri.2023.0031","article-title":"Glymphatic Magnetic Resonance Imaging: Part I\u2014Methodologies for Evaluation of the Glymphatic System","volume":"27","author":"Lee","year":"2023","journal-title":"Investig. Magn. Reson. Imaging"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.neuroimage.2018.12.026","article-title":"Non-Invasive MRI of Brain Clearance Pathways Using Multiple Echo Time Arterial Spin Labelling: An Aquaporin-4 Study","volume":"188","author":"Ohene","year":"2019","journal-title":"Neuroimage"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Alghanimy, A., Martin, C., Gallagher, L., and Holmes, W.M. (2023). The Effect of a Novel AQP4 Facilitator, TGN-073, on Glymphatic Transport Captured by Diffusion MRI and DCE-MRI. 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