Article Text

PDF

162
EFFECT OF TYSABRI AND AQP4-IGG ON AN IN-VITRO MODEL OF BBB
  1. Conor McQuaid1,
  2. Anu Jacob2,
  3. Adjanie Patabendige1
  1. 1The University of Liverpool
  2. 2The Walton Centre

Abstract

Background Neuromyelitis Optica (NMO) is an inflammatory, astrocytopathic, demyelinating disease of the CNS mediated by anti AQP4-IgG that targets the AQP4 protein, the dominant water channel on astrocyte foot processes at the blood brain barrier (BBB). Natalizimumab (NTZ, Tysabri) prevents migration of activated T lymphocytes across the BBB and is effective in preventing inflammation in MS. However, for unknown reasons, NTZ worsens NMO, precipitating relapses. We explored the effect of NTZ on a model of BBB.

Methods Using an in-vitro culture model of BBB (Human Brain Endothelial Cells (HBEC) and Human Astrocytes) tightness of HBEC layer was measured using Trans-Endothelial Electrical Resistance (TEER).

Results Addition of NTZ to the model caused TEER values to reduce significantly compared to control. Addition of AQP4-IgG and NTZ caused further significant reduction of TEER. Addition of just the AQP4-IgG did not have any effect.

Conclusion NTZ apparently lowers surrogate measures of BBB integrity in the presence of AQP4-IgG. Whether this in vitro effect translates to easier access of AQP4-IgG to the AQP4 in-vivo or predisposes to attacks is uncertain and is being explored.

  • EPILEPSY

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.