HaloTrace: A spatiotemporally precise fluorescent readout of blood-brain barrier permeability in mice.

ABSTRACT: The blood-brain barrier (BBB) is an indispensable, selectively permeable interface that controls the entry and exit of nutrients, ions and waste products into the brain. Despite its biological importance, most measurements of BBB permeability rely on dyes that suffer from nonspecific signals, lack of spatial fidelity, and incompatibility with longitudinal or repeated measurements. Here we present HaloTrace: a method which leverages the HaloTag ligand-receptor tool to generate a precise spatiotemporal readout of BBB integrity that avoids major pitfalls of existing methods. We present evidence that the fluorescent HaloTag ligand has minimal interactions with blood contents but can enter the brain specifically at sites of BBB dysfunction, where it covalently binds to nearby HaloTag receptors.

SUBMITTER: Zucker HL 

PROVIDER: S-EPMC12636304 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature