A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes.
By Shinsuke Nakagawa, M. Deli, H. Kawaguchi, T. Shimizudani, Takanori Shimono, Á. Kittel, Kunihiko Tanaka, M. Niwa. Neurochemistry International, 2009
651 citations recorded by the source corpus.
Blood-brain barrier (BBB) characteristics are induced and maintained by cross-talk between brain microvessel endothelial cells and neighbouring elements of the neurovascular unit. While pericytes are the cells situated closest to brain endothelial cells morphologically and share a common basement membrane, they have not been used in co-culture BBB models for testing drug permeability. We have developed and characterized a new syngeneic BBB model using primary cultures of the three main cell types of cerebral microvessels. The co-culture of endothelial cells, pericytes and astrocytes mimick the anatomical situation in vivo. In the presence of both pericytes and astrocytes rat brain endothelial cells expressed enhanced levels of tight junction (TJ) proteins occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. Further morphological evidence of the presence of interendothelial TJs was provided by electron microscopy. The transendothelial electrical resistance (TEER) of brain endothelial monolayers in triple co-culture, indicating the tightness of TJs reached 400Omegacm(2) on average, while the endothelial permeability coefficients (P(e)) for fluorescein was in the range of 3x10(-6)cm/s. Brain endothelial cells in the new model expressed glucose transporter-1, efflux transporters P-glycoprotein and multidrug resistance protein-1, and showed a polarized transport of rhodamine 123, a ligand for P-glycoprotein. To further characterize the model, drug permeability assays were performed using a set of 19 compounds with known in vivo BBB permeability. Good correlation (R(2)=0.89) was found between in vitroP(e) values obtained from measurements on the BBB model and in vivo BBB permeability data. The new BBB model, which is the first model to incorporate pericytes in a triple co-culture setting, can be a useful tool for research on BBB physiology and pathology and to test candidate compounds for centrally acting drugs.
Subfields: Neurology, Oncology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/8736aa2c45ccbea2f8f8cd8701de6c0ceb99bb03
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Citations in the corpus
- Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. (2011, background): “This conclusion is based on in vitro coculture studies where pericytes were shown to increase the transendothelial electrical resistance (TEER) of endothelial cell monolayers (Al Ahmad et al., 2009; Dohgu et al., 2005; Hayashi et al., 2004; Hori et al., 2004; Nakagawa et al., 2009).”
- A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics (2022, background): “The endothelial cells are further linked to a continuous barrier through inter-endothelial junctions, restricting the transport of water-soluble substances [69,70].”
- Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier (2015, neutral): “Although the molecular weight of NaF is low ( M W : 376.27), it cannot significantly permeate the intact BBB 19 .”
- Structure and function of the blood-brain barrier. (2010, background): “More recently, induction by pericytes, neurons and cells of monocyte lineage has also been described (Abbott et al., 2006; Nakagawa et al., 2009).”