title: A novel brain neurovascular unit model with neurons, astrocytes and microvascular endothelial cells of rat.
abstract: 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.
authors: College of Pharmaceutical Sciences & College of Chinese Medicine, Southwest University, Chongqing 400715, China.
authors: Qiang
authors: Q
authors: Xue
authors: Yang
authors: Y
authors: Liu
authors: Hongyi
authors: H
authors: Qi
authors: Qiang
authors: Q
authors: Ma
authors: Ling
authors: L
authors: Xu
authors: Weihai
authors: W
authors: Chen
authors: Gang
authors: G
authors: Chen
authors: Xiaoyu
authors: X
authors: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001812:Blood-Brain Barrier / Q000648:ultrastructure*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology*; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D019793:Fluorescein; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000166:cytology*; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006735:Horseradish Peroxidase; D019793:Fluorescein
keywords: anoxia-reoxygenation; astrocytes; brain microvascular endothelial cells; neurons.; neurovascular unit; triple cell co-culture model