{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:14:21Z","timestamp":1774350861827,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Inhibition of fatty acid synthesis (FAS) stimulates tumor cell death and reduces angiogenesis. When SH-SY5Y cells or primary neurons are exposed to hypoxia only, inhibition of FAS yields significantly enhanced cell injury. The pathophysiology of stroke, however, is not only restricted to hypoxia but also includes reoxygenation injury. Hence, an oxygen-glucose-deprivation (OGD) model with subsequent reoxygenation in both SH-SY5Y cells and primary neurons as well as a murine stroke model were used herein in order to study the role of FAS inhibition and its underlying mechanisms. SH-SY5Y cells and cortical neurons exposed to 10 h of OGD and 24 h of reoxygenation displayed prominent cell death when treated with the Acetyl-CoA carboxylase inhibitor TOFA or the fatty acid synthase inhibitor cerulenin. Such FAS inhibition reduced the reduction potential of these cells, as indicated by increased NADH<jats:sub>2<\/jats:sub><jats:sup>+<\/jats:sup>\/NAD<jats:sup>+<\/jats:sup> ratios under both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> stroke conditions. As observed in the OGD model, FAS inhibition also resulted in increased cell death in the stroke model. Stroke mice treated with cerulenin did not only display increased brain injury but also showed reduced neurological recovery during the observation period of 4 weeks. Interestingly, cerulenin treatment enhanced endothelial cell leakage, reduced transcellular electrical resistance (TER) of the endothelium and contributed to poststroke blood-brain barrier (BBB) breakdown. The latter was a consequence of the activated NF-\u03baB pathway, stimulating MMP-9 and ABCB1 transporter activity on the luminal side of the endothelium. In conclusion, FAS inhibition aggravated poststroke brain injury as consequence of BBB breakdown and NF-\u03baB-dependent inflammation.<\/jats:p>","DOI":"10.3389\/fncel.2021.733973","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T11:49:30Z","timestamp":1629114570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of Fatty Acid Synthesis Aggravates Brain Injury, Reduces Blood-Brain Barrier Integrity and Impairs Neurological Recovery in a Murine Stroke Model"],"prefix":"10.3389","volume":"15","author":[{"given":"Lisa","family":"Janssen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Ai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet B.","family":"Caglayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ertugrul","family":"Kilic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk M.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek","family":"Venkataramani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"B\u00e4hr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten R.","family":"Doeppner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.bbamcr.2003.10.013","article-title":"Bcl-2 family regulation of neuronal development and neurodegeneration.","volume":"1644","author":"Akhtar","year":"2004","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122375","article-title":"Molecular mechanisms of IL-33-mediated stromal interactions in cancer metastasis.","volume":"3","author":"Andersson","year":"2018","journal-title":"JCI Insight"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2294","article-title":"Isolation and Cultivation of Primary Brain Endothelial Cells from Adult Mice.","volume":"7","author":"Assmann","year":"2017","journal-title":"Bio Protoc."},{"key":"B4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/labinvest.2016.125","article-title":"Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model.","volume":"97","author":"Bastos","year":"2017","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00546","article-title":"Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.","volume":"10","author":"Brose","year":"2016","journal-title":"Front. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1111\/jnc.12617","article-title":"Fatty acid biosynthesis from glutamate and glutamine is specifically induced in neuronal cells under hypoxia.","volume":"129","author":"Brose","year":"2014","journal-title":"J. Neurochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1096\/fj.05-5404com","article-title":"Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor.","volume":"20","author":"Browne","year":"2006","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"866.e","DOI":"10.1016\/j.cmet.2018.07.019","article-title":"Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation.","volume":"28","author":"Bruning","year":"2018","journal-title":"Cell Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/jphp.12033","article-title":"Alteration in P-glycoprotein at the blood-brain barrier in the early period of MCAO in rats.","volume":"65","author":"Cen","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5065","DOI":"10.3390\/nu7075065","article-title":"Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt\/NF-kB\/MMP-9 Pathway.","volume":"7","author":"Chiu","year":"2015","journal-title":"Nutrients"},{"key":"B11","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/jcbfm.2013.217","article-title":"Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia.","volume":"34","author":"Chu","year":"2014","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"B12","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/978-1-4939-0320-7_34","article-title":"In vitro models of the blood-brain barrier.","volume":"1135","author":"Czupalla","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1111\/j.1471-4159.1992.tb10055.x","article-title":"Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo models.","volume":"58","author":"Dehouck","year":"1992","journal-title":"J. Neurochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0166-2236(99)01401-0","article-title":"Pathobiology of ischaemic stroke: an integrated view.","volume":"22","author":"Dirnagl","year":"1999","journal-title":"Trends Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.nbd.2010.05.033","article-title":"Transplantation of TAT-Bcl-xL-transduced neural precursor cells: Long-term neuroprotection after stroke.","volume":"40","author":"Doeppner","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.5966\/sctm.2015-0078","article-title":"Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression.","volume":"4","author":"Doeppner","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00338","article-title":"Effects of neural progenitor cells on post-stroke neurological impairment - a detailed and comprehensive analysis of behavioral tests.","volume":"8","author":"Doeppner","year":"","journal-title":"Front. Cell. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/jcbfm.2010.211","article-title":"Acute hepatocyte growth factor treatment induces long-term neuroprotection and stroke recovery via mechanisms involving neural precursor cell proliferation and differentiation.","volume":"31","author":"Doeppner","year":"2011","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1038\/jcbfm.2013.126","article-title":"TAT-Hsp70 induces neuroprotection against stroke via anti-inflammatory actions providing appropriate cellular microenvironment for transplantation of neural precursor cells.","volume":"33","author":"Doeppner","year":"2013","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1386","DOI":"10.1038\/cddis.2014.359","article-title":"Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.","volume":"5","author":"Doeppner","year":"","journal-title":"Cell Death Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.1093\/brain\/aws269","article-title":"The novel proteasome inhibitor BSc2118 protects against cerebral ischaemia through HIF1A accumulation and enhanced angioneurogenesis.","volume":"135","author":"Doeppner","year":"2012","journal-title":"Brain"},{"key":"B22","doi-asserted-by":"publisher","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-brain barrier model for drug permeability studies.","volume":"10","author":"Eigenmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"B23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1750-3639.2011.00517.x","article-title":"Liver X receptor activation enhances blood-brain barrier integrity in the ischemic brain and increases the abundance of ATP-binding cassette transporters ABCB1 and ABCC1 on brain capillary cells.","volume":"22","author":"ElAli","year":"2012","journal-title":"Brain Pathol. Zurich Switz."},{"key":"B24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/s0006-8993(99)01843-0","article-title":"Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion.","volume":"842","author":"Fujimura","year":"1999","journal-title":"Brain Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1158\/0008-5472.CAN-07-2489","article-title":"Fatty Acid Synthase Gene Is Up-regulated by Hypoxia via Activation of Akt and Sterol Regulatory Element Binding Protein-1.","volume":"68","author":"Furuta","year":"2008","journal-title":"Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/BF02570903","article-title":"The effct of cerulenin on sterol biosynthesis in Saccharomyces cerevisiae.","volume":"12","author":"Greenspan","year":"1977","journal-title":"Lipids"},{"key":"B27","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1749-6632.2010.05735.x","article-title":"NF-\u03baB and innate immunity in ischemic stroke.","volume":"1207","author":"Harari","year":"2010","journal-title":"Ann. N Y. Acad. Sci."},{"key":"B28","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-642-17972-3","author":"Heinrich","year":"2014","journal-title":"L\u00f6ffler\/Petrides Biochemie und Pathobiochemie."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3791\/2445","article-title":"Detection of functional matrix metalloproteinases by zymography.","volume":"2010","author":"Hu","year":"2010","journal-title":"J. Vis. Exp. JoVE"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1111\/jphp.12122","article-title":"Modulation of P-glycoprotein in rat brain microvessel endothelial cells under oxygen glucose deprivation.","volume":"65","author":"Ji","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":".e9","DOI":"10.1016\/j.urology.2012.02.046","article-title":"Inhibition of Fatty-acid Synthase Suppresses P-AKT and Induces Apoptosis in Bladder Cancer.","volume":"80","author":"Jiang","year":"2012","journal-title":"Urology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.brainres.2017.10.024","article-title":"Inhibiting 12\/15-lipoxygenase to treat acute stroke in permanent and tPA induced thrombolysis models.","volume":"1678","author":"Karatas","year":"2018","journal-title":"Brain Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/476974","article-title":"Regulations of P-Glycoprotein\/ABCB1\/ MDR1 in Human Cancer Cells.","volume":"2014","author":"Katayama","year":"2014","journal-title":"New J. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/ana.10356","article-title":"Intravenous TAT-Bcl-Xl is protective after middle cerebral artery occlusion in mice.","volume":"52","author":"Kilic","year":"2002","journal-title":"Ann. Neurol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3791\/54592","article-title":"An In Vitro Model of the Blood-brain Barrier Using Impedance Spectroscopy: A Focus on T Cell-endothelial Cell Interaction.","volume":"2016","author":"Kuzmanov","year":"2016","journal-title":"J. Vis. Exp."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00032","article-title":"Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke.","volume":"4","author":"Lakhan","year":"2013","journal-title":"Front. Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/clc.4960271404","article-title":"Pathophysiology and therapeutic targets for ischemic stroke.","volume":"27","author":"Levine","year":"2004","journal-title":"Clin. Cardiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10571-019-00654-y","article-title":"Myosin IIA Regulated Tight Junction in Oxygen Glucose-Deprived Brain Endothelial Cells Via Activation of TLR4\/PI3K\/Akt\/JNK1\/2\/14-3-3\u03b5\/NF-\u03baB\/MMP9 Signal Transduction Pathway.","volume":"39","author":"Lv","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1096\/fj.201700162R","article-title":"Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.","volume":"32","author":"Maherally","year":"2018","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"B40","first-page":"236","article-title":"Studies on cerulenin. I. Studies on cerulenin producing strain.","volume":"16","author":"Matsumae","year":"1963","journal-title":"J. Antibiot."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1111\/j.1349-7006.2010.01596.x","article-title":"Fatty acid synthase inhibitor cerulenin suppresses liver metastasis of colon cancer in mice.","volume":"101","author":"Murata","year":"2010","journal-title":"Cancer Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1007\/s11064-009-9943-6","article-title":"Reduction of brain infarction induced by a transient brain ischemia in mdr1a knockout mice.","volume":"34","author":"Murozono","year":"2009","journal-title":"Neurochem. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/jb\/mvz017","article-title":"Cellular and molecular mechanisms of sterile inflammation in ischaemic stroke.","volume":"165","author":"Nakamura","year":"2019","journal-title":"J. Biochem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nrc1588","article-title":"Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs.","volume":"5","author":"Nakanishi","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1093\/oxfordjournals.jbchem.a129827","article-title":"The action mechanism of cerulenin. I. Effect of cerulenin on sterol and fatty acid biosynthesis in yeast.","volume":"71","author":"Nomura","year":"1972","journal-title":"J. Biochem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1128\/mmbr.40.3.681-697.1976","article-title":"The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis.","volume":"40","author":"Omura","year":"1976","journal-title":"Bacteriol. Rev."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1161\/STROKEAHA.109.554824","article-title":"Plasma and brain matrix metalloproteinase-9 after acute focal cerebral ischemia in rats.","volume":"40","author":"Park","year":"2009","journal-title":"Stroke"},{"key":"B48","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1006\/bbrc.1997.6089","article-title":"Direct Interaction of the Mitochondrial Membrane Protein Carnitine Palmitoyltransferase I with Bcl-2.","volume":"231","author":"Paumen","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1161\/01.str.31.7.1686","article-title":"Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte infiltration in a rat model of focal cerebral ischemia.","volume":"31","author":"Phillips","year":"2000","journal-title":"Stroke"},{"key":"B50","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.brainres.2015.07.005","article-title":"Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.","volume":"1628","author":"Qosa","year":"2015","journal-title":"Brain Res."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3791\/50062","article-title":"An in vivo assay to test blood vessel permeability.","volume":"2013","author":"Radu","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B52","author":"Rassow","year":"2006","journal-title":"Biochemie: 50 Tabellen."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1177\/0271678X16655551","article-title":"Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers.","volume":"36","author":"Rempe","year":"2016","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.neuroscience.2008.07.007","article-title":"NF-kappaB signaling in cerebral ischemia.","volume":"158","author":"Ridder","year":"2009","journal-title":"Neuroscience"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3791\/50079","article-title":"Isolation and culture of mouse cortical astrocytes.","volume":"2013","author":"Schildge","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B56","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.ejphar.2017.09.042","article-title":"Fatty acid synthase modulates proliferation, metabolic functions and angiogenesis in hypoxic pulmonary artery endothelial cells.","volume":"815","author":"Singh","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.celrep.2015.01.037","article-title":"Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration.","volume":"10","author":"Song","year":"2015","journal-title":"Cell Rep."},{"key":"B58","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nn1676","article-title":"Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemia.","volume":"9","author":"Spudich","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.neuroscience.2012.03.036","article-title":"Matrix metalloproteinase-2 or \u22129 deletions protect against hemorrhagic transformation during early stage of cerebral ischemia and reperfusion.","volume":"212","author":"Suofu","year":"2012","journal-title":"Neuroscience"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1038\/nm.4181","article-title":"Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.","volume":"22","author":"Svensson","year":"2016","journal-title":"Nat. Med."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055166","article-title":"In vitro blood-brain barrier models using brain capillary endothelial cells isolated from neonatal and adult rats retain age-related barrier properties.","volume":"8","author":"Takata","year":"2013","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00056","article-title":"Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke.","volume":"10","author":"Turner","year":"2016","journal-title":"Front. Cell Neurosci."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-14-59","article-title":"Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.","volume":"14","author":"Watson","year":"2013","journal-title":"BMC Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/B978-0-12-803196-4.00011-4","article-title":"\u201cRole of Matrix Metalloproteinases in Brain Edema,\u201d in","author":"Yang","year":"2017","journal-title":"Brain Edema"},{"key":"B65","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1080\/01616412.2018.1460701","article-title":"Paracellular tightness and the functional expression of efflux transporters P-gp and BCRP in bEnd3 cells.","volume":"40","author":"Yang","year":"2018","journal-title":"Neurol. Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/ana.23734","article-title":"Inhibition of 12\/15-lipoxygenase as therapeutic strategy to treat stroke.","volume":"73","author":"Yigitkanli","year":"2013","journal-title":"Ann. Neurol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.2741\/2267","article-title":"Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia.","volume":"12","author":"Ying","year":"2007","journal-title":"Front. Biosci. J. Virtual Libr."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1093\/carcin\/bgu042","article-title":"Cancer cell-associated fatty acid synthase activates endothelial cells and promotes angiogenesis in colorectal cancer.","volume":"35","author":"Zaytseva","year":"2014","journal-title":"Carcinogenesis"},{"key":"B69","doi-asserted-by":"publisher","first-page":"7696","DOI":"10.4238\/2015.July.13.15","article-title":"Neuroprotective effects of Bcl-2 overexpression on nerve cells of rats with acute cerebral infarction.","volume":"14","author":"Zhang","year":"2015","journal-title":"Genet. Mol. Res. GMR"},{"key":"B70","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/s0165-0270(97)00065-4","article-title":"Zymographic measurement of gelatinase activity in brain tissue after detergent extraction and affinity-support purification.","volume":"76","author":"Zhang","year":"1997","journal-title":"J. Neurosci. Methods"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1161\/ATVBAHA.120.315031","article-title":"Neural Progenitor Cell-Derived Extracellular Vesicles Enhance Blood-Brain Barrier Integrity by NF-\u03baB (Nuclear Factor-\u03baB)-Dependent Regulation of ABCB1 (ATP-Binding Cassette Transporter B1) in Stroke Mice.","volume":"41","author":"Zhang","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1160\/th05-07-0477","article-title":"Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator.","volume":"95","author":"Zhang","year":"2006","journal-title":"Thromb. Haemost."},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7994","article-title":"Dephosphorylation and mitochondrial translocation of cofilin sensitizes human leukemia cells to cerulenin-induced apoptosis via the ROCK1\/Akt\/JNK signaling pathway.","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"B74","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/jcbfm.2009.228","article-title":"Mutant ubiquitin-mediated beta-secretase stability via activation of caspase-3 is related to beta-amyloid accumulation in ischemic striatum in rats.","volume":"30","author":"Zhang","year":"2010","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1046\/j.1471-4159.2003.01756.x","article-title":"Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity: Bcl-2 protects neurons in the infarct margin.","volume":"85","author":"Zhao","year":"2003","journal-title":"J. Neurochem."},{"key":"B76","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/sj.bjc.6603350","article-title":"Fatty acid synthase: a novel target for antiglioma therapy.","volume":"95","author":"Zhao","year":"2006","journal-title":"Br. J. Cancer"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.733973\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T11:49:35Z","timestamp":1629114575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.733973\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":76,"alternative-id":["10.3389\/fncel.2021.733973"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2021.733973","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]},"article-number":"733973"}}