Mimicking Marker Spread After Disruption of the Blood–Brain Barrier with a Collagen-Based Hydrogel Phantom

Abstract

Recent studies of the spread of substances penetrating the disrupted blood–brain barrier have revealed that the spread in the parenchyma surrounding a vessel has a complex character. In particular, a flow-like motion occurred for a short time that exhibits a smooth transition to diffusional spread. To address the possible physical background of such behavior, we created a system formed by a hydrogel medium with a channel filled by a marker solution, which can serve as a physical model mimicking the process of a substance passively spreading to the brain’s parenchyma when the blood–brain barrier is disrupted. The key result obtained in this work consists of the conclusion that the above-mentioned two-stage character of the spread process discovered in a previous biophysical experiment on the blood–brain opening in a living mouse may originate from the specificity of transport in porous soft matter with relaxation. We propose a mathematical model based on the extended Cattaneo equation, which reproduces our experimental data; determines the crossover time coinciding with that found in the biological system; and, therefore, provides a means of interpretation of this phenomenon.

Keywords

• blood–brain barrier
• parenchyma
• microfluidics
• phantom studies
• Cattaneo equation
• hydrogels