In vitro blood-brain barrier (BBB) models have important applications in the study of neurological diseases. New models could provide in-depth insight into the understanding of cellular and molecular mechanisms underlying BBB establishment. They could also have great benefits in the development of new drugs and delivery systems for a broad range of diseases affecting the brain.
Session Chair: Professor Roxana O Carare MD, PhD
Professor of Clinical Neuroanatomy, Equality and Diversity Lead (University of Southampton)
Roxana Carare is a medically qualified Professor of Clinical Neuroanatomy and experimental neuropathology in the University of Southampton. Having graduated in general medicine in 1994 in Bucharest, Roxana completed her PhD in experimental neuropathology in 2006, in the University of Southampton, UK. The main international recognition for Roxana Carare has come from the neuroanatomy and neuropathology interdisciplinary research she leads, demonstrating the unique lymphatic drainage pathways by which fluid and soluble amyloid are eliminated from the brain along basement membranes within the walls of cerebral capillaries and arteries (Intramural Periarterial Drainage Pathways, IPAD).
The focus of Roxana’s research is to manipulate the intramural periarterial drainage pathways to improve the clearance of amyloid and interstitial fluid from the ageing brain, preventing neurodegenerative and neurovascular diseases.
Diem, A., Macgregor Sharp, M., Gatherer, M., Bressloff, N., Carare, R-O., & Richardson, G. (2017). Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage. Frontiers in Neuroscience, 11, .
Wojtas, A., Kang, S., Olley, B., Gatherer, M., Shinohara, M., Lozano, P., ... Fryer, J. D. (2017). Loss of Clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways. Proceedings of National Academy of Sciences of the United States of America (PNAS), 114(33), E6962-E6971. DOI: 10.1073/pnas.1701137114
Diem, A. K., Tan, M., Bressloff, N. W., Hawkes, C., Morris, A. W. J., Weller, R. O., & Carare, R. O. (2016). A simulation model of periarterial clearance of amyloid-beta from the brain. Frontiers in Aging Neuroscience, 1-30. DOI: 10.3389/fnagi.2016.00018
Keable, A., Fenna, K., Yuen, H. M., Johnston, D. A., Smyth, N. R., Smith, C., ... Carare, R-O. (2016). Deposition of amyloid-beta in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1862(5), 1037-1046. DOI: 10.1016/j.bbadis.2015.08.024
Manousopoulou, A., Saito, S., Yamamoto, Y., Al-Daghri, N. M., Ihara, M., Carare, R. O., & Garbis, S. D. (2016). Hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer’s disease mouse model. Journal of Alzheimer's Disease, 51(2), 333-338. DOI: 10.3233/JAD-151078
Innervation of cerebral arteries is key to maintenance of efficient clearance and flow. This project funded by Alzheimer’s Research UK in collaboration with Dr Cheryl Hawkes (Open University) tests the hypothesis that loss of perivascular innervation by cholinergic neurons leads to dysfunctional regulation of vascular tone, thereby reducing the motive force for perivascular drainage of Aβ leading to a worsening of cerebral amyloid angiopathy. Researcher: Mrs Maureen Gatherer
Using novel nanoparticles produced in-house, with funding from BBSRC project grant we have investigated the capacity of the perivascular drainage pathways and demonstrated that particles of 20nm-1micrometre cannot drain along the intramural perivascular drainage pathways, suggesting these pathways are limited to the elimination of fluid and not cells.
With funding from Biogen, we are currently defining the fine anatomical pathways for the communication between cerebrospinal fluid and the cerebral parenchyma. Researcher: Nazira Albargothy.
What papers are we looking for?
We are looking for a wide variety of papers on this topic to provide an academic and industry perspective.
Neurological diseases range from diseases with
1) intracellular accumulation of proteins, such as Dementia with Lewy Bodies or Parkinson’s disease
2) extracellular accumulation of proteins such as Alzheimer’s disease, cerebral amyloid angiopathy
3) cerebrovascular ischaemia or haemorrhages (stroke)
4) trauma, as well as many others. There is no effective curative treatment for any of these diseases.
Clinical trials are effective if there is a robust preclinical programme behind them. There are limitations imposed by animal models as they only replicate some parts of the pathological features and experimental work takes long to complete. In order to increase efficiency and specificity of experimental neuropathology leading to efficient treatments, better in vitro models are required. Using induced pluripotent stem cell (iPSCs) lines as well as immortalised cerebral cell lines in combination with modern techniques that replicate the flow of blood or interstitial fluid in the brain represent an exciting and promising way forward. We invite submissions from groups working with a variety of nerve and glial cells and systems.
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