In Vitro Models of Central Nervous System Barriers for Blood-Brain Barrier Permeation Studies

Sounak Bagchi, Behnaz Lahooti, Tanya Chhibber, Sree pooja Varahachalam, Rahul Mittal, Abhijeet Joshi, Rahul Dev Jayant

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

One of the biggest challenging diseases are the neurodegenerative diseases which are not easy to target due to the presence of a complex semipermeable, dynamic, and adaptable barrier between the central nervous system (CNS) and the systemic circulation termed as the blood-brain barrier (BBB), which controls the exchange of molecules. Its semipermeable nature restricts the movement of bigger molecules, like drugs, across it and leads to minimal bioavailability of drugs in the CNS. This poses the biggest shortcoming in the development of therapeutics for CNS disorders. Although the complexity of the BBB muddles the drug delivery approaches into the CNS and can promote disease progression, understanding the composition and functions of BBB provides a platform for unraveling the way toward drug development. The BBB is comprised of brain microvascular endothelial CNS cells which communicate with other CNS cells (astrocytes, pericytes) and behave according to the state of the CNS, by retorting against pathological environments and modulating disease progression. This chapter discusses the fundamentals of BBB, permeation mechanisms, an overview of different in vitro BBB models with their advantages and disadvantages, and rationale of selecting penetration prediction methods toward the important role in the development of CNS therapeutics.

Original languageEnglish (US)
Title of host publicationNeuromethods
PublisherHumana Press Inc.
Pages235-253
Number of pages19
DOIs
StatePublished - 2021

Publication series

NameNeuromethods
Volume157
ISSN (Print)0893-2336
ISSN (Electronic)1940-6045

Keywords

  • Astrocytes
  • Blood-brain barrier (BBB)
  • Brain microvascular endothelial cells (BMECs)
  • Central nervous system
  • In vitro BBB models
  • Pericytes
  • Tight junctions

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Psychiatry and Mental health

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