{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:20:55Z","timestamp":1777609255145,"version":"3.51.4"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071330"],"award-info":[{"award-number":["82071330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Transient ischemic attack (TIA) has been widely regarded as a clinical entity. Even though magnetic resonance imaging (MRI) results of TIA patients are negative, potential neurovascular damage might be present, and may account for long-term cognitive impairment. Animal models that simulate human diseases are essential tools for in-depth study of TIA. Previous studies have clarified that Dl-3-N-butylphthalide (NBP) promotes angiogenesis after stroke. However, the effects of NBP on TIA remain unknown. This study aims to develop an optimized TIA model in C57BL\/6 mice to explore the microscopic evidence of ischemic injury after TIA, and investigate the therapeutic effects of NBP on TIA. C57BL\/6 mice underwent varying durations (7, 8, 9 or 10\u00a0min) of middle cerebral artery occlusion (MCAO). Cerebral artery occlusion and reperfusion were assessed by laser speckle contrast imaging. TIA and ischemic stroke were distinguished by neurological testing and MRI examination at 24\u00a0h post-operation. Neuronal apoptosis was examined by TUNEL staining. Images of submicron cerebrovascular networks were obtained <jats:italic>via<\/jats:italic> micro-optical sectioning tomography. Subsequently, the mice were randomly assigned to a sham-operated group, a vehicle-treated TIA group or an NBP-treated TIA group. Vascular density was determined by immunofluorescent staining and fluorescein isothiocyanate method, and the expression of angiogenic growth factors were detected by western blot analysis. We found that an 8-min or shorter period of ischemia induced neither permanent neurological deficits nor MRI detectable brain lesions in C57BL\/6 mice, but histologically caused neuronal apoptosis and cerebral vasculature abnormalities. NBP treatment increased the number of CD31<jats:sup>+<\/jats:sup> microvessels and perfused microvessels after TIA. NBP also up-regulated the expression of VEGF, Ang-1 and Ang-2 and improved the cerebrovascular network. In conclusion, 8\u00a0min or shorter cerebral ischemia induced by the suture MCAO method is an appropriate TIA model in C57BL\/6 mice, which conforms to the definition of human TIA, but causes microscopic neurovascular impairment. NBP treatment increased the expression of angiogenic growth factors, promoted angiogenesis and improved cerebral microvessels after TIA. Our study provides new insights on the pathogenesis and potential treatments of TIA.<\/jats:p>","DOI":"10.3389\/fphar.2021.751397","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T04:41:55Z","timestamp":1632890515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Dl-3-N-Butylphthalide Promotes Angiogenesis in an Optimized Model of Transient Ischemic Attack in C57BL\/6 Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Jiahui","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaigai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhouping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1097\/01.WCB.0000122745.72175.D5","article-title":"Laser Speckle Flowmetry for the Study of Cerebrovascular Physiology in normal and Ischemic Mouse Cortex","volume":"24","author":"Ayata","year":"2004","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/jcbfm.2013.188","article-title":"Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease","volume":"34","author":"Baron","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/jcbfm.1993.87","article-title":"Mouse Strain Differences in Susceptibility to Cerebral Ischemia Are Related to Cerebral Vascular Anatomy","volume":"13","author":"Barone","year":"1993","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.neurol.2015.07.013","article-title":"Epidemiology of Stroke and Transient Ischemic Attacks: Current Knowledge and Perspectives","volume":"172","author":"B\u00e9jot","year":"2016","journal-title":"Rev. Neurol. (Paris)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1038\/jcbfm.2008.76","article-title":"Transcriptomic Screening of Microvascular Endothelial Cells Implicates Novel Molecular Regulators of Vascular Dysfunction after Spinal Cord Injury","volume":"28","author":"Benton","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B6","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1161\/STROKEAHA.110.603647","article-title":"Early Predictive Biomarkers for Lesion after Transient Cerebral Ischemia","volume":"42","author":"Berthet","year":"2011","journal-title":"Stroke"},{"key":"B7","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1161\/STROKEAHA.117.019276","article-title":"Transient Ischemic Attack Results in Delayed Brain Atrophy and Cognitive Decline","volume":"49","author":"Bivard","year":"2018","journal-title":"Stroke"},{"key":"B8","first-page":"796","article-title":"Effects of Chiral 3-N-Butylphthalide on Apoptosis Induced by Transient Focal Cerebral Ischemia in Rats","volume":"24","author":"Chang","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"B9","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1179\/1743132814Y.0000000451","article-title":"The Effect of a Microcatheter-Based Selective Intra-arterial Hypothermia on Hemodynamic Changes Following Transient Cerebral Ischemia","volume":"37","author":"Chen","year":"2015","journal-title":"Neurol. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/00006123-199603000-00021","article-title":"Procedural and Strain-Related Variables Significantly Affect Outcome in a Murine Model of Focal Cerebral Ischemia","volume":"38","author":"Connolly","year":"1996","journal-title":"Neurosurgery"},{"key":"B11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.brainres.2017.03.010","article-title":"TIA Model Is Attainable in Wistar Rats by Intraluminal Occlusion of the MCA for 10min or Shorter","volume":"1663","author":"Durukan Tolvanen","year":"2017","journal-title":"Brain Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1161\/STROKEAHA.108.192218","article-title":"Definition and Evaluation of Transient Ischemic AttackThe American Academy of Neurology Affirms the Value of This Statement as an Educational Tool for Neurologists","volume":"40","author":"Easton","year":"2009","journal-title":"Stroke"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1161\/STROKEAHA.114.007581","article-title":"Cortical Selective Neuronal Loss, Impaired Behavior, and normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks","volume":"46","author":"Ejaz","year":"2015","journal-title":"Stroke"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1161\/STROKEAHA.111.643130","article-title":"Depression and Antidepressant Use after Stroke and Transient Ischemic Attack","volume":"43","author":"El Husseini","year":"2012","journal-title":"Stroke"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.07.035","article-title":"Reduced Severity of Outcome of Recurrent Ipsilateral Transient Cerebral Ischemia Compared with Contralateral Transient Cerebral Ischemia in Rats","volume":"26","author":"Fan","year":"2017","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3583","DOI":"10.1364\/BOE.8.003583","article-title":"Plastic Embedding Immunolabeled Large-Volume Samples for Three-Dimensional High-Resolution Imaging","volume":"8","author":"Gang","year":"2017","journal-title":"Biomed. Opt. Express"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1161\/01.str.28.11.2303","article-title":"Incomplete Infarct and Delayed Neuronal Death after Transient Middle Cerebral Artery Occlusion in Rats","volume":"28","author":"Garcia","year":"1997","journal-title":"Stroke"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/S1474-4422(07)70274-0","article-title":"Risk of Stroke Early after Transient Ischaemic Attack: a Systematic Review and Meta-Analysis","volume":"6","author":"Giles","year":"2007","journal-title":"Lancet Neurol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3791\/61673","article-title":"Quantification of Cerebral Perfusion Using Laser Speckle Imaging and Infarct Volume Using MRI in a Pre-clinical Model of Posterior Circulation Stroke","volume":"165","author":"Gnyawali","year":"2020","journal-title":"J. Vis. Exp."},{"key":"B20","doi-asserted-by":"publisher","first-page":"12142","DOI":"10.1038\/ncomms12142","article-title":"High-throughput Dual-Colour Precision Imaging for Brain-wide Connectome with Cytoarchitectonic Landmarks at the Cellular Level","volume":"7","author":"Gong","year":"2016","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/0306-4522(93)90343-e","article-title":"Differential Vulnerability in the Hindbrain Neurons and Local Cerebral Blood Flow during Bilateral Vertebral Occlusion in Gerbils","volume":"56","author":"Hata","year":"1993","journal-title":"Neuroscience"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneumeth.2006.01.028","article-title":"A New Model of Thromboembolic Stroke in the Posterior Circulation of the Rat","volume":"156","author":"Henninger","year":"2006","journal-title":"J. Neurosci. Methods"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1212\/01.wnl.0000129482.70315.2f","article-title":"The High Risk of Stroke Immediately after Transient Ischemic Attack: a Population-Based Study","volume":"62","author":"Hill","year":"2004","journal-title":"Neurology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0140-6736(07)60150-0","article-title":"Validation and Refinement of Scores to Predict Very Early Stroke Risk after Transient Ischaemic Attack","volume":"369","author":"Johnston","year":"2007","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3995\/jstroke.8.1","article-title":"Experimental Studies of Ischemic Brain Edema","volume":"8","author":"Koizumi","year":"1986","journal-title":"Jpn. J. Stroke"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1126\/science.1191776","article-title":"Micro-optical Sectioning Tomography to Obtain a High-Resolution Atlas of the Mouse Brain","volume":"330","author":"Li","year":"2010","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1007\/s11011-018-0307-2","article-title":"L-3-n-Butylphthalide Reduces Ischemic Stroke Injury and Increases M2 Microglial Polarization","volume":"33","author":"Li","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s12021-019-09434-x","article-title":"Brain-Wide Shape Reconstruction of a Traced Neuron Using the Convex Image Segmentation Method","volume":"18","author":"Li","year":"2020","journal-title":"Neuroinformatics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.brainres.2009.06.018","article-title":"Enhanced Angiogenesis with Dl-3n-Butylphthalide Treatment after Focal Cerebral Ischemia in RHRSP","volume":"1289","author":"Liao","year":"2009","journal-title":"Brain Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jns.2007.04.025","article-title":"dl-3n-butylphthalide Prevents Stroke via Improvement of Cerebral Microvessels in RHRSP","volume":"260","author":"Liu","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1161\/01.str.20.1.84","article-title":"Reversible Middle Cerebral Artery Occlusion without Craniectomy in Rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"B32","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/s40064-015-1102-8","article-title":"Regulation of the Microvascular Circulation in the Leg Muscles, Pancreas and Small Intestine in Rats","volume":"4","author":"Maeda","year":"2015","journal-title":"Springerplus"},{"key":"B33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.brainres.2003.10.028","article-title":"Extension of Cerebral Hypoperfusion and Ischaemic Pathology beyond MCA Territory after Intraluminal Filament Occlusion in C57Bl\/6J Mice","volume":"997","author":"Mccoll","year":"2004","journal-title":"Brain Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jneumeth.2011.08.002","article-title":"A New Method for Visualization of Endothelial Cells and Extravascular Leakage in Adult Mouse Brain Using Fluorescein Isothiocyanate","volume":"202","author":"Miyata","year":"2011","journal-title":"J. Neurosci. Methods"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1111\/ene.12469","article-title":"Fatigue, Psychological and Cognitive Impairment Following Transient Ischaemic Attack and Minor Stroke: a Systematic Review","volume":"21","author":"Moran","year":"2014","journal-title":"Eur. J. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/BF00310662","article-title":"A New Model of Brainstem Ischemia by Embolization Technique in Cats","volume":"14","author":"Nakahara","year":"1991","journal-title":"Neurosurg. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/0006-8993(95)00033-m","article-title":"The Role of Strain\/vendor Differences on the Outcome of Focal Ischemia Induced by Intraluminal Middle Cerebral Artery Occlusion in the Rat","volume":"675","author":"Oliff","year":"1995","journal-title":"Brain Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/NEN.0b013e3181cd331c","article-title":"An Optimized Mouse Model for Transient Ischemic Attack","volume":"69","author":"Pedrono","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B39","first-page":"85","article-title":"Differential Binding of the Lectins Griffonia Simplicifolia I and Lycopersicon esculentum to Microvascular Endothelium: Organ-specific Localization and Partial Glycoprotein Characterization","volume":"51","author":"Porter","year":"1990","journal-title":"Eur. J. Cell Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1001\/archneurol.2010.320","article-title":"Perfusion Computed Tomography in Transient Ischemic Attack","volume":"68","author":"Prabhakaran","year":"2011","journal-title":"Arch. Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.3174\/ajnr.A3551","article-title":"Perfusion Deficits Detected by Arterial Spin-Labeling in Patients with TIA with Negative Diffusion and Vascular Imaging","volume":"34","author":"Qiao","year":"2013","journal-title":"AJNR Am. J. Neuroradiol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1177\/0271678X18776833","article-title":"Dl-3-N-butylphthalide Attenuates Ischemic Reperfusion Injury by Improving the Function of Cerebral Artery and Circulation","volume":"39","author":"Qin","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B43","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nmeth.3662","article-title":"NeuroGPS-Tree: Automatic Reconstruction of Large-Scale Neuronal Populations with Dense Neurites","volume":"13","author":"Quan","year":"2016","journal-title":"Nat. Methods"},{"key":"B44","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00418-014-1301-3","article-title":"Use of Labeled Tomato Lectin for Imaging Vasculature Structures","volume":"143","author":"Robertson","year":"2015","journal-title":"Histochem. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1212\/01.WNL.0000152985.32732.EE","article-title":"Timing of TIAs Preceding Stroke: Time Window for Prevention Is Very Short","volume":"64","author":"Rothwell","year":"2005","journal-title":"Neurology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1161\/01.str.29.10.2162","article-title":"A Critical Reevaluation of the Intraluminal Thread Model of Focal Cerebral Ischemia: Evidence of Inadvertent Premature Reperfusion and Subarachnoid Hemorrhage in Rats by Laser-Doppler Flowmetry","volume":"29","author":"Schmid-Elsaesser","year":"1998","journal-title":"Stroke"},{"key":"B47","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1017\/s0317167100017248","article-title":"Factors Associated with Cognitive Decline in Transient Ischemic Attack Patients","volume":"41","author":"Sivakumar","year":"2014","journal-title":"Can. J. Neurol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1097\/00004647-199907000-00005","article-title":"Focal Ischemic Preconditioning Induces Rapid Tolerance to Middle Cerebral Artery Occlusion in Mice","volume":"19","author":"Stagliano","year":"1999","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B49","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.expneurol.2014.07.004","article-title":"Transient Ischemia Elicits a Sustained Enhancement of Thrombus Development in the Cerebral Microvasculature: Effects of Anti-thrombotic Therapy","volume":"261","author":"Tang","year":"2014","journal-title":"Exp. Neurol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1161\/01.str.29.4.850","article-title":"A Novel Endothelin Antagonist, A-127722, Attenuates Ischemic Lesion Size in Rats with Temporary Middle Cerebral Artery Occlusion: a Diffusion and Perfusion MRI Study","volume":"29","author":"Tatlisumak","year":"1998","journal-title":"Stroke"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1111\/ene.13088","article-title":"Ongoing Impairments Following Transient Ischaemic Attack: Retrospective Cohort Study","volume":"23","author":"Turner","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1161\/STROKEAHA.114.005205","article-title":"Persistent Cognitive Impairment after Transient Ischemic Attack","volume":"45","author":"van Rooij","year":"2014","journal-title":"Stroke"},{"key":"B53","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s13760-020-01295-5","article-title":"Animal Models of Transient Ischemic Attack: a Review","volume":"120","author":"Wang","year":"2020","journal-title":"Acta Neurol. Belg."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1212\/WNL.0000000000001665","article-title":"Prevalence, Knowledge, and Treatment of Transient Ischemic Attacks in China","volume":"84","author":"Wang","year":"2015","journal-title":"Neurology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/cercor\/bhu166","article-title":"Direct 3D Analyses Reveal Barrel-specific Vascular Distribution and Cross-Barrel Branching in the Mouse Barrel Cortex","volume":"26","author":"Wu","year":"2016","journal-title":"Cereb. Cortex"},{"key":"B56","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroimage.2013.10.036","article-title":"3D BrainCV: Simultaneous Visualization and Analysis of Cells and Capillaries in a Whole Mouse Brain with One-Micron Voxel Resolution","volume":"87","author":"Wu","year":"2014","journal-title":"Neuroimage"},{"key":"B57","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3389\/fnana.2017.00128","article-title":"Precise Cerebral Vascular Atlas in Stereotaxic Coordinates of Whole Mouse Brain","volume":"11","author":"Xiong","year":"2017","journal-title":"Front. Neuroanat."},{"key":"B58","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1097\/01.WCB.0000107730.66603.51","article-title":"Vascular Endothelial Growth Factor Induces Abnormal Microvasculature in the Endoglin Heterozygous Mouse Brain","volume":"24","author":"Xu","year":"2004","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B59","first-page":"433","article-title":"Inhibitory Effects of Chiral 3-N-Butylphthalide on Inflammation Following Focal Ischemic Brain Injury in Rats","volume":"21","author":"Xu","year":"2000","journal-title":"Acta Pharmacol. Sin."},{"key":"B60","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.1007\/s11064-017-2328-3","article-title":"L-3-n-Butylphthalide Activates Akt\/mTOR Signaling, Inhibits Neuronal Apoptosis and Autophagy and Improves Cognitive Impairment in Mice with Repeated Cerebral Ischemia-Reperfusion Injury","volume":"42","author":"Xu","year":"2017","journal-title":"Neurochem. Res."},{"key":"B61","first-page":"117","article-title":"Effects of Dl-3-N-Butylphthalide on Regional Cerebral Blood Flow in Right Middle Cerebral Artery Occlusion Rats","volume":"19","author":"Yan","year":"1998","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"B62","doi-asserted-by":"publisher","first-page":"964","DOI":"10.14336\/AD.2019.0608","article-title":"Dl-3-n-butylphthalide Reduces Neurovascular Inflammation and Ischemic Brain Injury in Mice","volume":"10","author":"Yang","year":"2019","journal-title":"Aging Dis."},{"key":"B63","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/cns.12438","article-title":"L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats","volume":"21","author":"Yang","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"B64","doi-asserted-by":"publisher","first-page":"948","DOI":"10.3969\/j.issn.1673-5374.2012.12.012","article-title":"Hypoxia Inducible Factor-1alpha Mediates protection of DL-3-N-Butylphthalide in Brain Microvascular Endothelial Cells against Oxygen Glucose Deprivation-Induced Injury","volume":"7","author":"Yang","year":"2012","journal-title":"Neural Regen. Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/01.WCB.0000096063.84070.C1","article-title":"A Model of Global Cerebral Ischemia in C57 BL\/6 Mice","volume":"24","author":"Yonekura","year":"2004","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B66","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jns.2014.10.022","article-title":"Enriched Environment Induces Angiogenesis and Improves Neural Function Outcomes in Rat Stroke Model","volume":"347","author":"Yu","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jep.2016.01.028","article-title":"PI3K\/Akt Pathway Contributes to Neuroprotective Effect of Tongxinluo against Focal Cerebral Ischemia and Reperfusion Injury in Rats","volume":"181","author":"Yu","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1159\/000339682","article-title":"Arterial Spin Labeling Imaging Findings in Transient Ischemic Attack Patients: Comparison with Diffusion- and Bolus Perfusion-Weighted Imaging","volume":"34","author":"Zaharchuk","year":"2012","journal-title":"Cerebrovasc. Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1080\/00207454.2019.1692835","article-title":"Effects of Butylphthalide Injection on Treatment of Transient Ischemic Attack as Shown by Diffusion-Weighted Magnetic Resonance Imaging Abnormality","volume":"130","author":"Zhang","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1093\/nsr\/nwz124","article-title":"High-resolution Mapping of Brain Vasculature and its Impairment in the hippocampus of Alzheimer's Disease Mice","volume":"6","author":"Zhang","year":"2019","journal-title":"Natl. Sci. Rev."},{"key":"B71","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s12031-018-1227-7","article-title":"Non-invasive Vagus Nerve Stimulation Protects against Cerebral Ischemia\/Reperfusion Injury and Promotes Microglial M2 Polarization via Interleukin-17A Inhibition","volume":"67","author":"Zhao","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s12021-020-09484-6","article-title":"GTree: an Open-Source Tool for Dense Reconstruction of Brain-wide Neuronal Population","volume":"19","author":"Zhou","year":"2020","journal-title":"Neuroinform"},{"key":"B73","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1111\/cns.13104","article-title":"Dl-3-N-butylphthalide Promotes Angiogenesis and Upregulates Sonic Hedgehog Expression after Cerebral Ischemia in Rats","volume":"25","author":"Zhou","year":"","journal-title":"CNS Neurosci. Ther."},{"key":"B74","doi-asserted-by":"publisher","first-page":"4947","DOI":"10.1096\/fj.201801706RR","article-title":"Sema3E\/PlexinD1 Signaling Inhibits Postischemic Angiogenesis by Regulating Endothelial DLL4 and Filopodia Formation in a Rat Model of Ischemic Stroke","volume":"33","author":"Zhou","year":"","journal-title":"FASEB J."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.751397\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T04:42:02Z","timestamp":1632890522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.751397\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":74,"alternative-id":["10.3389\/fphar.2021.751397"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.751397","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]},"article-number":"751397"}}