{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:27:47Z","timestamp":1793320067011,"version":"4.5.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"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>2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine <jats:italic>Ligusticum chuanxiong Hort<\/jats:italic>. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reactivity to facilitate neurovascular restoration in the subacute ischemic stroke needs to be urgently verified. In this research, permanent occlusion of the middle cerebral artery (MCAO) model was conducted and TMP (10, 20, 40 mg\/kg) was intraperitoneally administrated to rats once daily for 2 weeks. Neurological function was evaluated by motor deficit score (MDS). Magnetic resonance imaging (MRI) was implemented to analyze tissue injury and cerebral blood flow (CBF). Magnetic resonance angiography (MRA) was applied to exhibit vascular signals. Transmission electron microscopy (TEM) was performed to detect the neurovascular unit (NVU) ultrastructure. Haematoxylin and eosin (HE) staining was utilized to evaluate cerebral histopathological lesions. The neurogenesis, angiogenesis, A1\/A2 reactivity, aquaporin 4 (AQP4) and connexin 43 (Cx43) of astrocytes were observed with immunofluorescent staining. Then FGF2\/PI3K\/AKT signals were measured by western blot. Findings revealed TMP ameliorated neurological functional recovery, preserved NVU integrity, and enhanced endogenous neurogenesis and angiogenesis of rats with subacute ischemia. Shifting A1 to A2 reactivity, suppressing excessive AQP4 and Cx43 expression of astrocytes, and activating FGF2\/PI3K\/AKT pathway might be potential mechanisms of promoting neurovascular restoration with TMP after ischemic stroke.<\/jats:p>","DOI":"10.3389\/fncel.2023.1125412","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:52:45Z","timestamp":1679896365000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1\/A2 reactive astrocytes"],"prefix":"10.3389","volume":"17","author":[{"given":"Xue-feng","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-cong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-yue","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-zhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-ming","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-feng","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neulet.2014.03.073","article-title":"Neuroprotective effect of aquaporin-4 deficiency in a mouse model of severe global cerebral ischemia produced by transient 4-vessel occlusion","volume":"574","author":"Akdemir","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1161\/01.str.29.9.1917","article-title":"Intracerebral hemorrhage in the rat: effects of hematoma aspiration","volume":"29","author":"Altumbabic","year":"1998","journal-title":"Stroke"},{"key":"B3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1023\/b:nere.0000014830.06376.e6","article-title":"Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection","volume":"29","author":"Bambrick","year":"2004","journal-title":"Neurochem. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3389\/fnmol.2017.00088","article-title":"The role of astrocytes in neuroprotection after brain stroke: potential in cell therapy","volume":"10","author":"Becerra-Calixto","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8563","DOI":"10.1007\/s12035-018-0992-1","article-title":"Recovery of neurovascular unit integrity by CDK5-KD astrocyte transplantation in a global cerebral ischemia model","volume":"55","author":"Becerra-Calixto","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12860-016-0120-x","article-title":"Gap junctions and hemichannels: communicating cell death in neurodevelopment and disease","volume":"18","author":"Belousov","year":"2017","journal-title":"BMC Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.jep.2014.10.019","article-title":"The combination of astragalus membranaceus and ligustrazine ameliorates micro-haemorrhage by maintaining blood-brain barrier integrity in cerebrally ischaemic rats","volume":"158","author":"Cai","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1161\/01.str.25.8.1651","article-title":"Correlation between angiogenesis and basic fibroblast growth factor expression in experimental brain infarct","volume":"25","author":"Chen","year":"1994","journal-title":"Stroke"},{"key":"B9","first-page":"104","article-title":"Ischemic postconditioning for stroke treatment: current experimental advances and future directions","volume":"3","author":"Chen","year":"2020","journal-title":"Cond. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/01.WCB.0000044631.80210.3C","article-title":"Astrocytes and brain injury","volume":"23","author":"Chen","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.brainresbull.2018.12.009","article-title":"Inhibition of Connexin43 hemichannels with Gap19 protects cerebral ischemia\/reperfusion injury via the JAK2\/STAT3 pathway in mice","volume":"146","author":"Chen","year":"2019","journal-title":"Brain Res. Bull."},{"key":"B12","doi-asserted-by":"publisher","first-page":"24334","DOI":"10.1038\/s41598-021-03694-x","article-title":"Cx43 carboxyl terminal domain determines AQP4 and Cx30 endfoot organization and blood brain barrier permeability","volume":"11","author":"Cibelli","year":"2021","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.2174\/138945013804806479","article-title":"A key role for connexin hemichannels in spreading ischemic brain injury","volume":"14","author":"Davidson","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"B14","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1365-2796.2009.02199.x","article-title":"The neurovascular unit in the setting of stroke","volume":"267","author":"del Zoppo","year":"2010","journal-title":"J. Intern. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.4103\/1673-5374.306064","article-title":"Astrocytes: a double-edged sword in neurodegenerative diseases","volume":"16","author":"Ding","year":"2021","journal-title":"Neural Regen. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"851746","DOI":"10.3389\/fphar.2022.851746","article-title":"Magnetic resonance imaging investigation of neuroplasticity after ischemic stroke in tetramethylpyrazine-treated rats","volume":"13","author":"Feng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.mcn.2010.05.007","article-title":"Inhibition of cytokine-induced connexin43 hemichannel activity in astrocytes is neuroprotective","volume":"45","author":"Froger","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.3390\/cells11101707","article-title":"Central nervous system pericytes contribute to health and disease","volume":"11","author":"Girolamo","year":"2022","journal-title":"Cells"},{"key":"B19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ejphar.2019.04.028","article-title":"Tetramethylpyrazine attenuates blood-brain barrier disruption in ischemia\/ reperfusion injury through the JAK\/STAT signaling pathway","volume":"854","author":"Gong","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/bjc.2013.694","article-title":"Increased microvascular proliferation is negatively correlated to tumour blood flow and is associated with unfavourable outcome in endometrial carcinomas","volume":"110","author":"Haldorsen","year":"2014","journal-title":"Br. J. Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1177\/0271678X16629976","article-title":"The blood-brain barrier after stroke: structural studies and the role of transcytotic vesicles","volume":"37","author":"Haley","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B22","doi-asserted-by":"publisher","first-page":"16","DOI":"10.4103\/1673-5374.264442","article-title":"Angiogenesis and neuronal remodeling after ischemic stroke","volume":"15","author":"Hatakeyama","year":"2020","journal-title":"Neural Regen. Res."},{"key":"B23","first-page":"456","article-title":"Assessment of the collateral function of the circle of Willis: three-dimensional time-of-flight MR angiography compared with transcranial color-coded duplex sonography","volume":"24","author":"Hoksbergen","year":"2003","journal-title":"Am. J. Neuroradiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3390\/ijms17050679","article-title":"Mechanism of mitochondrial connexin43\u2019s protection of the neurovascular unit under acute cerebral ischemia-reperfusion injury","volume":"17","author":"Hou","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2321797","DOI":"10.1155\/2018\/2321797","article-title":"Blood-brain barrier damage as the starting point of leukoaraiosis caused by cerebral chronic hypoperfusion and its involved mechanisms: effect of agrin and Aquaporin-4","volume":"2018","author":"Huang","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/2045-8118-11-15","article-title":"Increased blood-brain barrier permeability and alterations in perivascular astrocytes and pericytes induced by intracisternal glutaric acid","volume":"11","author":"Isasi","year":"2014","journal-title":"Fluids Barriers CNS"},{"key":"B27","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13054-016-1190-z","article-title":"Prediction of mortality and functional outcome from status epilepticus and independent external validation of STESS and EMSE scores","volume":"20","author":"Kang","year":"2016","journal-title":"Crit. Care"},{"key":"B28","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.neuroimage.2011.12.055","article-title":"Monitoring blood flow alterations in the Tg2576 mouse model of Alzheimer\u2019s disease by in vivo magnetic resonance angiography at 17.6 T","volume":"60","author":"Kara","year":"2012","journal-title":"Neuroimage"},{"key":"B29","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1096\/fj.13-231274","article-title":"Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia","volume":"28","author":"Katada","year":"2014","journal-title":"FASEB J."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4029","DOI":"10.1242\/jcs.035758","article-title":"AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells","volume":"121","author":"Kong","year":"2008","journal-title":"J. Cell Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"732820","DOI":"10.3389\/fcell.2021.732820","article-title":"The \u201cneuro-glial-vascular\u201d unit: the role of glia in neurovascular unit formation and dysfunction","volume":"9","author":"Kugler","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"664","DOI":"10.14336\/AD.2018.0720","article-title":"Reactive astrocytes in neurodegenerative diseases","volume":"10","author":"Li","year":"2019","journal-title":"Aging Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.3389\/fphys.2019.01528","article-title":"MRI evaluation of axonal remodeling after combination treatment with xiaoshuan enteric-coated capsule and enriched environment in rats after ischemic stroke","volume":"10","author":"Li","year":"2019","journal-title":"Front. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1159\/000467141","article-title":"Aquaporin-4 mediates the suppressive effect of lipopolysaccharide on hippocampal neurogenesis","volume":"23","author":"Liang","year":"2016","journal-title":"Neuroimmunomodulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.neulet.2004.09.013","article-title":"Tetramethylpyrazine reduces ischemic brain injury in rats","volume":"372","author":"Liao","year":"2004","journal-title":"Neurosci. Lett."},{"key":"B36","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive astrocytes: production, function and therapeutic potential","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"B37","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1161\/01.str.0000037675.97888.9d","article-title":"Dynamic changes in cerebral blood flow and angiogenesis after transient focal cerebral ischemia in rats. Evaluation with serial magnetic resonance imaging","volume":"33","author":"Lin","year":"2002","journal-title":"Stroke"},{"key":"B40","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.pneurobio.2015.09.008","article-title":"Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke","volume":"144","author":"Liu","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"8280","DOI":"10.1073\/pnas.1205880109","article-title":"Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex","volume":"109","author":"Liu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B41","doi-asserted-by":"publisher","first-page":"103881","DOI":"10.1016\/j.mvr.2019.103881","article-title":"Imbalanced serum levels of Ang1, Ang2 and VEGF in systemic sclerosis: integrated effects on microvascular reactivity","volume":"125","author":"Michalska-Jakubus","year":"2019","journal-title":"Microvasc. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3390\/ijms20030571","article-title":"Dual roles of astrocyte-derived factors in regulation of blood-brain barrier function after brain damage","volume":"20","author":"Michinaga","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1002\/glia.23814","article-title":"The effects of A1\/A2 astrocytes on oligodendrocyte linage cells against white matter injury under prolonged cerebral hypoperfusion","volume":"68","author":"Miyamoto","year":"2020","journal-title":"Glia"},{"key":"B45","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1177\/0271678X15608396","article-title":"Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice","volume":"36","author":"Nahirney","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B46","doi-asserted-by":"publisher","first-page":"93","DOI":"10.2463\/mrms.2014-0132","article-title":"The technical and clinical features of 3D-FLAIR in neuroimaging","volume":"14","author":"Naiganawa","year":"2015","journal-title":"Magn. Reson. Med. Sci."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2022-0049","article-title":"Molecular mediators of angiogenesis and neurogenesis after ischemic stroke","author":"Paro","year":"2022","journal-title":"Rev. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1159\/000431129","article-title":"Ocular angiogenesis: vascular endothelial growth factor and other factors","volume":"55","author":"Rubio","year":"2016","journal-title":"Dev. Ophthalmol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1159\/000495457","article-title":"Tetraparesis following an anterior circulation stroke: a case report","volume":"10","author":"Saleh","year":"2018","journal-title":"Case Rep. Neurol."},{"key":"B50","first-page":"121","article-title":"The rat cortex in stereotaxic coordinates","volume":"27","author":"Schober","year":"1986","journal-title":"J. Hirnforsch."},{"key":"B51","doi-asserted-by":"publisher","first-page":"50","DOI":"10.2174\/1389200221666201019143252","article-title":"Tumor angiogenesis and VEGFR-2: mechanism, pathways and current biological therapeutic interventions","volume":"22","author":"Shah","year":"2021","journal-title":"Curr. Drug Metab."},{"key":"B53","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3389\/fnins.2018.00582","article-title":"Inhibitive effects of FGF2\/FGFR1 pathway on astrocyte-mediated inflammation in vivo and in vitro after infrasound exposure","volume":"12","author":"Shi","year":"2018","journal-title":"Front. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e101624","DOI":"10.1371\/journal.pone.0101624","article-title":"Pathological alterations and stress responses near DBS electrodes after MRI scans at 7.0T, 3.0T and 1.5T: an in vivo comparative study","volume":"9","author":"Shi","year":"2014","journal-title":"PLoS One"},{"key":"B54","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.bbr.2013.11.034","article-title":"Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats","volume":"260","author":"Tamakoshi","year":"2014","journal-title":"Behav. Brain Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.3892\/etm.2015.2365","article-title":"Ligustrazine reduces blood-brain barrier permeability in a rat model of focal cerebral ischemia and reperfusion","volume":"9","author":"Tan","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13041-018-0387-2","article-title":"Stimulation-induced structural changes at the nucleus, endoplasmic reticulum and mitochondria of hippocampal neurons","volume":"11","author":"Tao-Cheng","year":"2018","journal-title":"Mol. Brain"},{"key":"B57","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12974-021-02176-1","article-title":"Brain gray matter astroglia-specific connexin 43 ablation attenuates spinal cord inflammatory demyelination","volume":"18","author":"Une","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.3390\/ijms21051603","article-title":"Regulation of AQP4 in the central nervous system","volume":"21","author":"Vandebroek","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"4474","DOI":"10.7150\/thno.31942","article-title":"Astrocytic connexin 43 potentiates myelin injury in ischemic white matter disease","volume":"9","author":"Wang","year":"2019","journal-title":"Theranostics"},{"key":"B60","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1177\/0963689718771889","article-title":"Enhanced neurogenesis and collaterogenesis by sodium danshensu treatment after focal cerebral ischemia in mice","volume":"27","author":"Wei","year":"2018","journal-title":"Cell Transplant."},{"key":"B61","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.neuropharm.2014.01.016","article-title":"Significance of higher-order chromatin architecture for neuronal function and dysfunction","volume":"80","author":"Wilczynski","year":"2014","journal-title":"Neuropharmacology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1177\/1073858408329509","article-title":"Agrin, aquaporin-4 and astrocyte polarity as an important feature of the blood-brain barrier","volume":"15","author":"Wolburg","year":"2009","journal-title":"Neuroscientist"},{"key":"B63","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1179\/174313209X414533","article-title":"Neuroprotection and enhanced neurogenesis by tetramethylpyrazine in adult rat brain after focal ischemia","volume":"32","author":"Xiao","year":"2010","journal-title":"Neurol. Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/ana.22386","article-title":"Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion","volume":"70","author":"Xie","year":"2011","journal-title":"Ann. Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.3892\/mmr.2014.3000","article-title":"Akt regulates beta-catenin in a rat model of focal cerebral ischemia-reperfusion injury","volume":"11","author":"Xing","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"B66","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12974-015-0245-4","article-title":"Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia\/macrophage activation during recovery","volume":"12","author":"Yang","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B67","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.neuro.2013.09.002","article-title":"Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats","volume":"39","author":"Yu","year":"2013","journal-title":"Neurotoxicology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"811","DOI":"10.3389\/fnins.2018.00811","article-title":"Multicellular crosstalk between exosomes and the neurovascular unit after cerebral ischemia. Therapeutic implications","volume":"12","author":"Zagrean","year":"2018","journal-title":"Front. Neurosci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.expneurol.2017.08.011","article-title":"Microglia and macrophages differ in their inflammatory profile after permanent brain ischemia","volume":"301","author":"Zarruk","year":"2018","journal-title":"Exp. Neurol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"105091","DOI":"10.1016\/j.nbd.2020.105091","article-title":"The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats","volume":"146","author":"Zhan","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B72","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1177\/0963689718802755","article-title":"Effects of xiaoshuan enteric-coated capsule on white and gray matter injury evaluated by diffusion tensor imaging in ischemic stroke","volume":"28","author":"Zhang","year":"2019","journal-title":"Cell Transplant."},{"key":"B74","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1097\/00004647-200204000-00002","article-title":"Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia","volume":"22","author":"Zhang","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B73","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s12906-016-1184-z","article-title":"Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia","volume":"16","author":"Zhang","year":"2016","journal-title":"BMC Complement. Altern. Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1179\/016164109X12445616596562","article-title":"Angiopoietin 1 counteracts vascular endothelial growth factor-induced blood-brain barrier permeability and alleviates ischemic injury in the early stages of transient focal cerebral ischemia in rats","volume":"32","author":"Zhao","year":"2010","journal-title":"Neurol. Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.neulet.2018.10.002","article-title":"Combined use of bFGF\/EGF and all-trans-retinoic acid cooperatively promotes neuronal differentiation and neurite outgrowth in neural stem cells","volume":"690","author":"Zhao","year":"2019","journal-title":"Neurosci. Lett."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1125412\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:52:51Z","timestamp":1679896371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1125412\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":74,"alternative-id":["10.3389\/fncel.2023.1125412"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2023.1125412","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]},"article-number":"1125412"}}