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Therefore, the overall protection of the neurovascular unit (NVU) is a promising therapeutic strategy for various neurovascular diseases. However, the complexity of the NVU limits the study of the pathological mechanisms of neurovascular dysfunction. Reconstituting the in vitro NVU is important for the pathological study and drug screening of neurovascular diseases. In this study, we generated a spontaneously assembled three\u2010dimensional NVU (3D NVU) by employing the primary neural stem cells and brain microvascular endothelial cells in a Matrigel extracellular matrix platform. This novel model exhibits the fundamental structures and features of the NVU, including neurons, astrocytes, oligodendrocytes, vascular\u2010like structures, and blood\u2013brain barrier\u2010like characteristics. Additionally, under oxygen\u2010glucose deprivation, the 3D NVU exhibits the neurovascular\u2010 or oxidative stress\u2010related pathological characteristics of cerebral ischemia and the injuries can be mitigated, respectively, by supplementing with the vascular endothelial growth factor or edaravone, which demonstrated that the availability of 3D NVU in ischemic stroke modeling. Finally, the 3D NVU promoted the angiogenesis and neurogenesis in the brain of cerebral ischemia rats. We expect that the proposed in vitro 3D NVU model will be widely used to investigate the relationships between angiogenesis and neurogenesis and to study the pathology and pharmacology of neurovascular diseases.<\/jats:p>","DOI":"10.1111\/bpa.12940","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T04:59:14Z","timestamp":1613278754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Reconstituting neurovascular unit with primary neural stem cells and brain microvascular endothelial cells in three\u2010dimensional matrix"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3927-2156","authenticated-orcid":false,"given":"Hongjin","family":"Wang","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences &amp; Chinese Medicine Southwest University Chongqing China"},{"name":"Chongqing Key Laboratory of New Drug Screening from 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