Using zebrafish to study and visualize barriers of the CNS

Abstract

Blood–central nervous system (CNS) barriers are structures critical for maintaining neural homeostasis. While these barriers preserve a healthy brain environment, their physical and chemical properties create obstacles for efficacious CNS drug delivery and are compromised in various CNS disease states. Even though the blood–brain barrier (BBB) was discovered over a century ago, molecular mechanisms and interacting cell types necessary for BBB function and integrity have only recently become uncovered. Furthermore, the field of BBB biology could benefit from utilizing an innovative model system to dissect elements crucial for barrier properties. Uncovered molecular pathways could bring to light novel CNS drug delivery targets and prevent CNS disease progression. There has been a surge of zebrafish use in biomedical research over the past few decades, which has provided researchers a valuable animal model system to genetically and chemically study these barrier structures deep within the brain parenchyma. Here, I describe genetic, chemical, and histology methods for utilizing zebrafish in studying blood–CNS barriers such as the BBB and how these zebrafish assays could be used to exploit the unanswered questions that remain in CNS barrier biology.