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Optimisation of a flow-based human in vitro blood–brain barrier model to replace animal models for studying immunopathogenesis of viral brain infections

Dr Adjanie Patabendige

At a glance

Award date
September 2012 - July 2016
Grant amount
Principal investigator
Dr Adjanie Patabendige
University of Liverpool


  • Replacement
Read the abstract
View the grant profile on GtR



This project aims to develop a human cell-culture model of the blood–brain barrier, to replace the use of some animal studies.


Encephalitis (inflammation and swelling of the brain) can be caused by a range of viruses, and the results are usually devastating. The blood‒brain barrier (BBB) is the specialised barrier that prevents viruses, bacteria and toxins from entering the brain, and a number of studies have implicated a disruption of the BBB during encephalitis. However, most studies of the BBB are done in animals or animal cell lines; most commonly rat and mouse models. These animals have symptoms such as leg paralysis, hunched back, and seizures following infection. A model of the BBB using human cells would represent an important scientific advance and replace the use of some animals used in BBB experiments.

Research details and methods

Building on existing 2D cultures, a 3D flow-based model which mimics blood flow in brain capillaries will be developed and characterised. Primary or immortalised human brain endothelial cells will be seeded on the blood side of the model and astrocytes or pericytes on the brain side. Serum from patients will be pumped over the cells and viruses will be introduced to the system to simulate infection and investigate the role of the BBB.


  1. Patabendige A et al (2018). Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model. Molecular and Cellular Neuroscience 89: 60-70. doi: 10.1016/j.mcn.2018.04.002
  2. Ferguson MC et al. (2015). Ability of the encephalitic arbovirus semliki forest virus to cross the blood-brain barrier is determined by the charge of the E2 glycoprotein. J Virol 89(15): 7536-49. doi: 10.1128/JVI.03645-14
  3. Patabendige A and Abbott NJ (2014). Primary porcine brain microvessel endothelial cell isolation and culture. Curr Protoc Neurosci 69: 3.27.1-17. doi: 10.1002/0471142301.ns0327s69
  4. Patabendige A. (2012). The value of in vitro blood-brain barrier models and their uses. ATLA 40:335-338. doi: 10.1177/026119291204000606
  5. Patabendige A. (2012). Toward a humanised alternative to the use of laboratory animals for blood-brain barrier research. ATLA 40, PiLAS 1(1):12-13. doi: 10.1177/026119291204000515