{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:14:50Z","timestamp":1790709290372,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2016R1A6A1A03011325"],"award-info":[{"award-number":["NRF-2016R1A6A1A03011325"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education","doi-asserted-by":"publisher","award":["RS-2023-00246603"],"award-info":[{"award-number":["RS-2023-00246603"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education","doi-asserted-by":"publisher","award":["RS-2024-00405900"],"award-info":[{"award-number":["RS-2024-00405900"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Government (MSIT)","award":["NRF-2016R1A6A1A03011325"],"award-info":[{"award-number":["NRF-2016R1A6A1A03011325"]}]},{"name":"Korean Government (MSIT)","award":["RS-2023-00246603"],"award-info":[{"award-number":["RS-2023-00246603"]}]},{"name":"Korean Government (MSIT)","award":["RS-2024-00405900"],"award-info":[{"award-number":["RS-2024-00405900"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Methamphetamine (METH) is a powerful addictive psychostimulant that gives rise to severe abusers worldwide. While many studies have reported on the neurotoxicity of METH, blood\u2013brain barrier (BBB) dysfunction has recently attracted attention as an essential target in METH-induced pathological changes in the brain. However, its mechanism has not been fully understood. We found that METH increased paracellular permeability and decreased vascular integrity through FITC\u2013dextran and trans-endothelial electrical resistance (TEER) assay in primary human brain endothelial cells (HBMECs). Also, redistribution of tight junction proteins (zonula occluden-1 and claudin-5) and reorganization of F-actin cytoskeleton were observed in METH-exposed HBMECs. To determine the mechanism of METH-induced BBB disruption, the RhoA\/ROCK signaling pathway was examined in METH-treated HBMECs. METH-activated RhoA, followed by an increase in the phosphorylation of downstream effectors, myosin light chain (MLC) and cofilin, occurs in HBMECs. Pretreatment with ROCK inhibitors Y-27632 and fasudil reduced the METH-induced increase in phosphorylation of MLC and cofilin, preventing METH-induced redistribution of junction proteins and F-actin cytoskeletal reorganization. Moreover, METH-induced BBB leakage was alleviated by ROCK inhibitors in vitro and in vivo. Taken together, these results suggest that METH induces BBB dysfunction by activating the RhoA\/ROCK signaling pathway, which results in the redistribution of junction proteins via F-actin cytoskeletal reorganization.<\/jats:p>","DOI":"10.3390\/biom15030340","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T03:37:57Z","timestamp":1740627477000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Involvement of RhoA\/ROCK Signaling Pathway in Methamphetamine-Induced Blood-Brain Barrier Disruption"],"prefix":"10.3390","volume":"15","author":[{"given":"Jong Su","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-3804","authenticated-orcid":false,"given":"Tam Thuy Lu","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hye","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyo Cheol","family":"Mun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4686-6179","authenticated-orcid":false,"given":"Eunyoung","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-7424","authenticated-orcid":false,"given":"Ji Hae","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.1523\/JNEUROSCI.22-20-08951.2002","article-title":"Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis","volume":"22","author":"Larsen","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1749-6632.1988.tb42104.x","article-title":"Neurotoxicity in dopamine and 5-hydroxytryptamine terminal fields: A regional analysis in nigrostriatal and mesolimbic projections","volume":"537","author":"Seiden","year":"1988","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12974-017-0825-6","article-title":"Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro","volume":"14","author":"Bortell","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1099","DOI":"10.1038\/cddis.2014.64","article-title":"Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor","volume":"5","author":"Ma","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.toxlet.2020.07.028","article-title":"Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4\/TRIF\/Peli1 signaling axis","volume":"333","author":"Yang","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/syn.20324","article-title":"High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus","volume":"60","author":"Bowyer","year":"2006","journal-title":"Synapse"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1161\/ATVBAHA.119.312461","article-title":"Methamphetamine Use and Cardiovascular Disease","volume":"39","author":"Kevil","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/j.1460-9568.2007.05741.x","article-title":"Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: Critical role of brain hyperthermia","volume":"26","author":"Kiyatkin","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Daneman, R., and Prat, A. (2015). The blood-brain barrier. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a020412"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/164_2020_404","article-title":"Structure and Function of the Blood-Brain Barrier (BBB)","volume":"273","author":"Benz","year":"2022","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1537-1891(02)00200-8","article-title":"Tight junctions of the blood-brain barrier: Development, composition and regulation","volume":"38","author":"Wolburg","year":"2002","journal-title":"Vascul Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1154641","DOI":"10.1080\/21688370.2016.1154641","article-title":"Junctional proteins of the blood-brain barrier: New insights into function and dysfunction","volume":"4","author":"Stamatovic","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sivandzade, F., Alqahtani, F., and Cucullo, L. (2020). Traumatic Brain Injury and Blood-Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082721"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bai, Y., Zhang, Y., Hua, J., Yang, X., Zhang, X., Duan, M., Zhu, X., Huang, W., Chao, J., and Zhou, R. (2016). Silencing microRNA-143 protects the integrity of the blood-brain barrier: Implications for methamphetamine abuse. Sci. Rep., 6.","DOI":"10.1038\/srep35642"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.brainres.2008.01.093","article-title":"Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse","volume":"1203","author":"Mahajan","year":"2008","journal-title":"Brain Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Northrop, N.A., and Yamamoto, B.K. (2015). Methamphetamine effects on blood-brain barrier structure and function. Front. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00069"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Turowski, P., and Kenny, B.A. (2015). The blood-brain barrier and methamphetamine: Open sesame?. Front. Neurosci., 9.","DOI":"10.3389\/fnins.2015.00156"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1142\/S0192415X18500283","article-title":"Protective Effects of Ginsenoside Rb1 against Blood-Brain Barrier Damage Induced by Human Immunodeficiency Virus-1 Tat Protein and Methamphetamine in Sprague-Dawley Rats","volume":"46","author":"Li","year":"2018","journal-title":"Am. J. Chin. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s12640-019-00156-1","article-title":"Protective Effects of Melatonin on Methamphetamine-Induced Blood-Brain Barrier Dysfunction in Rat Model","volume":"37","author":"Namyen","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.bbrc.2018.12.144","article-title":"Methamphetamine reduces expressions of tight junction proteins, rearranges F-actin cytoskeleton and increases the blood brain barrier permeability via the RhoA\/ROCK-dependent pathway","volume":"509","author":"Xue","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/ijmm.2014.1618","article-title":"Role of Rho kinase in lysophosphatidic acid-induced altering of blood-brain barrier permeability","volume":"33","author":"Yu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Feng, S., Zou, L., Wang, H., He, R., Liu, K., and Zhu, H. (2018). RhoA\/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier Permeability. Molecules, 23.","DOI":"10.3390\/molecules23092371"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.bbamem.2007.08.018","article-title":"Crosstalk of tight junction components with signaling pathways","volume":"1778","author":"Tapia","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","first-page":"16","article-title":"Rho signaling and tight junction functions","volume":"25","author":"Terry","year":"2010","journal-title":"Physiology (Bethesda)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/cm.20472","article-title":"Rho-kinase\/ROCK: A key regulator of the cytoskeleton and cell polarity","volume":"67","author":"Amano","year":"2010","journal-title":"Cytoskeleton (Hoboken)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1006\/excr.2000.5046","article-title":"Regulation and functions of Rho-associated kinase","volume":"261","author":"Amano","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/jnc.12681","article-title":"Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions","volume":"129","author":"Gibson","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1016\/j.febslet.2006.06.056","article-title":"Involvement of Rho\/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells","volume":"580","author":"Li","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19086","DOI":"10.1523\/JNEUROSCI.2508-13.2013","article-title":"Pharmacologic inhibition of ROCK2 suppresses amyloid-beta production in an Alzheimer\u2019s disease mouse model","volume":"33","author":"Herskowitz","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mulherkar, S., and Tolias, K.F. (2020). RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury. Cells, 9.","DOI":"10.3390\/cells9010245"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1161\/01.STR.0000181077.84981.11","article-title":"Inhibition of Rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection","volume":"36","author":"Rikitake","year":"2005","journal-title":"Stroke"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40478-016-0310-y","article-title":"Fasudil attenuates aggregation of alpha-synuclein in models of Parkinson\u2019s disease","volume":"4","author":"Tatenhorst","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.03.008","article-title":"ROCK inhibition in models of neurodegeneration and its potential for clinical translation","volume":"189","author":"Koch","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4103\/1673-5374.184499","article-title":"ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro","volume":"11","author":"Jia","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1471-4159.2007.04756.x","article-title":"Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo","volume":"103","author":"Lingor","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s10571-012-9845-z","article-title":"Rho-kinase inhibitor, fasudil, prevents neuronal apoptosis via the Akt activation and PTEN inactivation in the ischemic penumbra of rat brain","volume":"32","author":"Wu","year":"2012","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.drudis.2010.06.011","article-title":"Rho-kinase inhibition: A novel therapeutic target for the treatment of cardiovascular diseases","volume":"15","author":"Dong","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1161\/01.RES.0000251668.39526.c7","article-title":"Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease","volume":"99","author":"Nohria","year":"2006","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/FJC.0b013e3182a3718f","article-title":"Rho kinases in cardiovascular physiology and pathophysiology: The effect of fasudil","volume":"62","author":"Shi","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1101\/gad.309823.117","article-title":"Bridging barriers: A comparative look at the blood-brain barrier across organisms","volume":"32","author":"Pfau","year":"2018","journal-title":"Genes. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/507423a","article-title":"Preclinical research: Make mouse studies work","volume":"507","author":"Perrin","year":"2014","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/2045-8118-10-33","article-title":"Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC\/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood\u2013brain barrier model for drug permeability studies","volume":"10","author":"Eigenmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3892\/mmr.2014.2169","article-title":"Tetramethylpyrazine promotes the proliferation and migration of brain endothelial cells","volume":"10","author":"Zhang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.brainres.2015.07.033","article-title":"Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity","volume":"1624","author":"Parikh","year":"2015","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E1243","DOI":"10.1073\/pnas.1621174114","article-title":"Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood-brain barrier disruption after ischemic brain injury","volume":"114","author":"Shi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1523\/JNEUROSCI.4266-11.2012","article-title":"HIV-1 Tat triggers nuclear localization of ZO-1 via Rho signaling and cAMP response element-binding protein activation","volume":"32","author":"Zhong","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"33324","DOI":"10.1074\/jbc.M113.483487","article-title":"Methamphetamine-induced Occludin Endocytosis Is Mediated by the Arp2\/3 Complex-regulated Actin Rearrangement","volume":"288","author":"Park","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117917","DOI":"10.1016\/j.lfs.2020.117917","article-title":"GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood-brain barrier dysfunction","volume":"256","author":"Hwang","year":"2020","journal-title":"Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s12272-020-01284-5","article-title":"PBN inhibits a detrimental effect of methamphetamine on brain endothelial cells by alleviating the generation of reactive oxygen species","volume":"43","author":"Hwang","year":"2020","journal-title":"Arch. Pharmacal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1242\/jcs.03353","article-title":"Filamin links cell shape and cytoskeletal structure to Rho regulation by controlling accumulation of p190RhoGAP in lipid rafts","volume":"120","author":"Mammoto","year":"2007","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neuropharm.2012.08.021","article-title":"Methamphetamine-induced nitric oxide promotes vesicular transport in blood-brain barrier endothelial cells","volume":"65","author":"Martins","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4103\/0975-3583.74258","article-title":"The role of RhoA\/Rho kinase pathway in endothelial dysfunction","volume":"1","author":"Yao","year":"2010","journal-title":"J. Cardiovasc. Dis. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Soliman, M., Cho, E.H., Park, J.G., Kim, J.Y., Alfajaro, M.M., Baek, Y.B., Kim, D.S., Kang, M.I., Park, S.I., and Cho, K.O. (2018). Rotavirus-Induced Early Activation of the RhoA\/ROCK\/MLC Signaling Pathway Mediates the Disruption of Tight Junctions in Polarized MDCK Cells. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32352-y"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"De Luca, C., Colangelo, A.M., Virtuoso, A., Alberghina, L., and Papa, M. (2020). Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology Approach to the Complexity of Synaptic Plasticity in Health and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041539"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.brainres.2016.05.049","article-title":"Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells","volume":"1646","author":"Jumnongprakhon","year":"2016","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e01307-17","DOI":"10.1128\/AAC.01307-17","article-title":"Effects of HIV-1 Tat and Methamphetamine on Blood-Brain Barrier Integrity and Function In Vitro","volume":"61","author":"Patel","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Qie, X., Wen, D., Guo, H., Xu, G., Liu, S., Shen, Q., Liu, Y., Zhang, W., Cong, B., and Ma, C. (2017). Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood-Brain Barrier Damage. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00639"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/s12974-018-1385-0","article-title":"Methamphetamine neurotoxicity, microglia, and neuroinflammation","volume":"15","author":"Shaerzadeh","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/cm.20547","article-title":"Regulation of epithelial permeability by the actin cytoskeleton","volume":"68","author":"Rodgers","year":"2011","journal-title":"Cytoskeleton (Hoboken)"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"31003","DOI":"10.1074\/jbc.M504768200","article-title":"Mechanism of redox-mediated guanine nucleotide exchange on redox-active Rho GTPases","volume":"280","author":"Heo","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/ncb938","article-title":"Redox-dependent downregulation of Rho by Rac","volume":"5","author":"Nimnual","year":"2003","journal-title":"Nat. Cell Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:00Z","timestamp":1760028180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["biom15030340"],"URL":"https:\/\/doi.org\/10.3390\/biom15030340","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]}}}