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Int J Biol Sci 2013; 9(2):174-189. doi:10.7150/ijbs.5115

Research Paper

A Novel Brain Neurovascular Unit Model with Neurons, Astrocytes and Microvascular Endothelial Cells of Rat

Qiang Xue1, 2, 3, Yang Liu1, 2, 3, Hongyi Qi1, 2, 3, Qiang Ma1,2, 3, Ling Xu1, 2, 3, Weihai Chen4, Gang Chen5, Xiaoyu Xu1, 2, 3,✉

1. College of Pharmaceutical Sciences & College of Chinese Medicine, Southwest University, Chongqing 400715, China;
2. Chongqing Engineering Research Center for Pharmacological Evaluation, Chongqing 400715, China;
3. Institute of Chinese Medicine, Southwest University, Chongqing 400715, China;
4. College of Psychology, Southwest University, Chongqing 400715, China;
5. Research Center of Medical Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, China.


A novel triple cell neurovascular unit (NVU) model co-culturing with neurons, brain microvascular endothelial cells (BMECs) and astrocytes was established in this study for investigating the cerebral diseases and screening the candidates of therapeutic drug. We have first performed the cell identification and morphological characterization, analyzed the specific protein expression and determined the blood-brain barrier (BBB) function of the co-culture model under normal condition. Then, we further determined the BBB function, inflammation, cell injury and the variation of neuroprotective factor in this model after anoxia-reoxygenation. The results suggest that this model exhibited a better BBB function and significantly increased expression of P-glycoprotein (Pg-P) and ZO-1 compared with BMECs only or co-culture with astrocytes or neurons. After anoxia-reoxygenation, the pathological changes of this model were basically resemblance to the pathological changes of brain cells and BBB in vivo. And nimodipine, an antagonist of calcium, could reverse those changes as well. According to our observations, we deduce that this triple cell co-culture model exhibits the basic structure, function and cell-cell interaction of NVU, which may offer a more proper in vitro system of NVU for the further investigation of cerebral diseases and drug screening.

Keywords: neurovascular unit, triple cell co-culture model, anoxia-reoxygenation, brain microvascular endothelial cells, astrocytes, neurons.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Xue Q, Liu Y, Qi H, Ma Q, Xu L, Chen W, Chen G, Xu X. A Novel Brain Neurovascular Unit Model with Neurons, Astrocytes and Microvascular Endothelial Cells of Rat. Int J Biol Sci 2013; 9(2):174-189. doi:10.7150/ijbs.5115. Available from