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Advances in in vitro modeling of the blood-brain barrier and neurovascular unit

© John J. Jamieson et al., 2019

In this thematic issue, Fluids and Barriers of the CNS aims to bring together papers related to in vitro modeling of the blood-brain barrier and the neurovascular unit (NVU). In recent years, major advances have been made in the field including the use of brain endothelial cells derived from human induced pluripotent stem cells, NVU models composed of multiple cell types, and the development of novel 3D models, including the use of microchips. Such advances are increasing our understanding of barrier function and intercellular crosstalk in health and disease, identification of therapeutic targets, and methods for high-throughput screenings of drugs for treatment of neurological diseases. 

This collection of articles has not been sponsored and articles have undergone the journal’s standard peer-review process.

  1. Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. It is an irreversible condition marked by irreversible cognitive loss, commonly attributed to the loss of hippocampal neurons due ...

    Authors: Snehal Raut, Ronak Patel and Abraham J. Al-Ahmad
    Citation: Fluids and Barriers of the CNS 2021 18:3
  2. In 2012, we provided the first published evidence that human pluripotent stem cells could be differentiated to cells exhibiting markers and phenotypes characteristic of the blood–brain barrier (BBB). In the en...

    Authors: Ethan S. Lippmann, Samira M. Azarin, Sean P. Palecek and Eric V. Shusta
    Citation: Fluids and Barriers of the CNS 2020 17:64
  3. In recent years, differentiation of human induced pluripotent stem cells (hiPSCs) into brain-specific microvascular endothelial cells (iBMECs) has frequently been used to model the blood–brain barrier (BBB). H...

    Authors: Pedram Motallebnejad and Samira M. Azarin
    Citation: Fluids and Barriers of the CNS 2020 17:54
  4. Predictive in vitro models of the human blood–brain barrier (BBB) are essential in early drug discovery and development. Among available immortalized human brain capillary endothelial cell lines (BCECs), the h...

    Authors: Birthe Gericke, Kerstin Römermann, Andreas Noack, Sandra Noack, Jessica Kronenberg, Ingolf Ernst Blasig and Wolfgang Löscher
    Citation: Fluids and Barriers of the CNS 2020 17:53
  5. Formation, maintenance, and repair of the blood–brain barrier (BBB) are critical for central nervous system homeostasis. The interaction of endothelial cells (ECs) with brain pericytes is known to induce BBB c...

    Authors: Marjolein Heymans, Ricardo Figueiredo, Lucie Dehouck, David Francisco, Yasuteru Sano, Fumitaka Shimizu, Takashi Kanda, Rémy Bruggmann, Britta Engelhardt, Peter Winter, Fabien Gosselet and Maxime Culot
    Citation: Fluids and Barriers of the CNS 2020 17:48
  6. The complexity of the blood–brain barrier (BBB) and neurovascular unit (NVU) was and still is a challenge to bridge. A highly selective, restrictive and dynamic barrier, formed at the interface of blood and br...

    Authors: Anuska V. Andjelkovic, Svetlana M. Stamatovic, Chelsea M. Phillips, Gabriela Martinez-Revollar and Richard F. Keep
    Citation: Fluids and Barriers of the CNS 2020 17:44
  7. The United States faces a national crisis involving opioid medications, where currently more than 130 people die every day. To combat this epidemic, a better understanding is needed of how opioids penetrate in...

    Authors: Jacquelyn A. Brown, Shannon L. Faley, Yajuan Shi, Kathleen M. Hillgren, Geri A. Sawada, Thomas K. Baker, John P. Wikswo and Ethan S. Lippmann
    Citation: Fluids and Barriers of the CNS 2020 17:38
  8. Pediatric diffuse intrinsic pontine glioma (DIPG) represents one of the most devastating and lethal brain tumors in children with a median survival of 12 months. The high mortality rate can be explained by the...

    Authors: Clémence Deligne, Johan Hachani, Sophie Duban-Deweer, Samuel Meignan, Pierre Leblond, Angel M. Carcaboso, Yasuteru Sano, Fumitaka Shimizu, Takashi Kanda, Fabien Gosselet, Marie-Pierre Dehouck and Caroline Mysiorek
    Citation: Fluids and Barriers of the CNS 2020 17:37
  9. The blood–brain barrier (BBB) plays an important role as a biological barrier by regulating molecular transport between circulating blood and the brain parenchyma. In drug development, the accurate evaluation ...

    Authors: Misaki Yamashita, Hiromasa Aoki, Tadahiro Hashita, Takahiro Iwao and Tamihide Matsunaga
    Citation: Fluids and Barriers of the CNS 2020 17:36
  10. The complexity of the neurovascular unit (NVU) poses a challenge in the investigations of drug transport across the blood–brain barrier (BBB) and the function of the brain capillary endothelium. Several in vit...

    Authors: C. Goldeman, B. Ozgür and B. Brodin
    Citation: Fluids and Barriers of the CNS 2020 17:32
  11. The most threatening metastases in breast cancer are brain metastases, which correlate with a very poor overall survival, but also a limited quality of life. A key event for the metastatic progression of breas...

    Authors: Carolin J. Curtaz, Constanze Schmitt, Saskia-Laureen Herbert, Jonas Feldheim, Nicolas Schlegel, Fabien Gosselet, Carsten Hagemann, Norbert Roewer, Patrick Meybohm, Achim Wöckel and Malgorzata Burek
    Citation: Fluids and Barriers of the CNS 2020 17:31
  12. Neuroimmune communication contributes to both baseline and adaptive physiological functions, as well as disease states. The vascular blood–brain barrier (BBB) and associated cells of the neurovascular unit (NV...

    Authors: Michelle A. Erickson, Miranda L. Wilson and William A. Banks
    Citation: Fluids and Barriers of the CNS 2020 17:26
  13. In vitro blood–brain barrier (BBB) models using human induced pluripotent stem (iPS) cell-derived brain microvascular endothelial-like cells (iBMELCs) have been developed to predict the BBB permeability of dru...

    Authors: Hiromasa Aoki, Misaki Yamashita, Tadahiro Hashita, Takahiro Iwao and Tamihide Matsunaga
    Citation: Fluids and Barriers of the CNS 2020 17:25
  14. The blood–brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the oth...

    Authors: Aditya Bhalerao, Farzane Sivandzade, Sabrina Rahman Archie, Ekram Ahmed Chowdhury, Behnam Noorani and Luca Cucullo
    Citation: Fluids and Barriers of the CNS 2020 17:22
  15. The blood–brain barrier (BBB) is altered in several diseases of the central nervous system. For example, the breakdown of the BBB during cerebral ischemia in stroke or traumatic brain injury is a hallmark of t...

    Authors: Anna Gerhartl, Nadja Pracser, Alexandra Vladetic, Sabrina Hendrikx, Heinz-Peter Friedl and Winfried Neuhaus
    Citation: Fluids and Barriers of the CNS 2020 17:19
  16. The endothelial cell–cell junctions of the blood–brain barrier (BBB) play a pivotal role in the barrier’s function. Altered cell–cell junctions can lead to barrier dysfunction and have been implicated in sever...

    Authors: Kelsey M. Gray, Jae W. Jung, Collin T. Inglut, Huang-Chiao Huang and Kimberly M. Stroka
    Citation: Fluids and Barriers of the CNS 2020 17:16
  17. The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell e...

    Authors: Hideaki Nishihara, Sasha Soldati, Adrien Mossu, Maria Rosito, Henriette Rudolph, William A. Muller, Daniela Latorre, Federica Sallusto, Mireia Sospedra, Roland Martin, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Fabien Gosselet and Britta Engelhardt
    Citation: Fluids and Barriers of the CNS 2020 17:3
  18. Blood–brain barrier dysfunction is associated with many late-stage neurodegenerative diseases. An emerging question is whether the mutations associated with neurodegenerative diseases can independently lead to...

    Authors: Moriah E. Katt, Lakyn N. Mayo, Shannon E. Ellis, Vasiliki Mahairaki, Jeffrey D. Rothstein, Linzhao Cheng and Peter C. Searson
    Citation: Fluids and Barriers of the CNS 2019 16:20
  19. Immune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential ...

    Authors: Shujun Ge, Xi Jiang, Debayon Paul, Li Song, Xiaofang Wang and Joel S. Pachter
    Citation: Fluids and Barriers of the CNS 2019 16:18
  20. Pericytes of the blood–brain barrier (BBB) are embedded within basement membrane between brain microvascular endothelial cells (BMECs) and astrocyte end-feet. Despite the direct cell–cell contact observed in v...

    Authors: John J. Jamieson, Raleigh M. Linville, Yuan Yuan Ding, Sharon Gerecht and Peter C. Searson
    Citation: Fluids and Barriers of the CNS 2019 16:15
  21. Brain endothelial cell-based in vitro models are among the most versatile tools in blood–brain barrier research for testing drug penetration to the central nervous system. Transcytosis of large pharmaceuticals...

    Authors: Andrea E. Toth, Simone S. E. Nielsen, Weronika Tomaka, N. Joan Abbott and Morten S. Nielsen
    Citation: Fluids and Barriers of the CNS 2019 16:14