Title:In Vitro Blood-Brain Barrier Models for Neuroinfectious Diseases: A
Narrative Review
Volume: 22
Issue: 8
Author(s): Ahmad Hussein Badawi, Nur Afiqah Mohamad, Johnson Stanslas, Brian Patrick Kirby, Vasantha Kumari Neela, Rajesh Ramasamy and Hamidon Basri*
Affiliation:
- Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang,
Selangor, Malaysia
Keywords:
Blood-brain barrier (BBB) model, standardization of BBB model, optimization parameters, validation parameters, neuroinfectious diseases, peripheral blood system, central nervous system.
Abstract: The blood-brain barrier (BBB) is a complex, dynamic, and adaptable barrier between the
peripheral blood system and the central nervous system. While this barrier protects the brain and spinal
cord from inflammation and infection, it prevents most drugs from reaching the brain tissue. With
the expanding interest in the pathophysiology of BBB, the development of in vitro BBB models has
dramatically evolved. However, due to the lack of a standard model, a range of experimental protocols,
BBB-phenotype markers, and permeability flux markers was utilized to construct in vitro BBB
models. Several neuroinfectious diseases are associated with BBB dysfunction. To conduct neuroinfectious
disease research effectively, there stems a need to design representative in vitro human BBB
models that mimic the BBB's functional and molecular properties. The highest necessity is for an in
vitro standardised BBB model that accurately represents all the complexities of an intact brain barrier.
Thus, this in-depth review aims to describe the optimization and validation parameters for building
BBB models and to discuss previous research on neuroinfectious diseases that have utilized in vitro
BBB models. The findings in this review may serve as a basis for more efficient optimisation, validation,
and maintenance of a structurally- and functionally intact BBB model, particularly for future
studies on neuroinfectious diseases.