Imaging contrast agent leakage in [T1-weighted] MRI would be an option, if you want to show a breakdown of the blood brain barrier over a period of time.

In case you have access to an optical imaging device, you could try i.v. injection of Cy5.5. With this protocol, you can even measure size-dependent break-down, as the fluorophore can be coupled to proteins of different sizes. Preparation of the tracer solution is quite straight-forward. You need to remove the hair at the mouse head beforehand, which works well with a commercial depilatory cream (from a normal drugstore), just with shorter incubation times (start with 30 s - 1 min) to avoid skin irritation.

The protocol is described very nicely in Chapter 29 of the following book:

Kursad Turksen (ed.), Permeability Barrier: Methods and Protocols, Methods in Molecular Biology, vol. 763, DOI 10.1007/978-1-61779-191-8_29

Dear Guiseppe,

keep in mind that BBB permeability can be highly dependent on the tracer you use. Size, charge and hydrophobicity of a tracer can definitely change their BBB permeability. E.g. small molecular weight tracers might pass paracellularly while larger do not. On the other hand, the paracellular passage could be unaltered but a change in transporter expression in endothelial cells could alter the transcellular passage of certain molecules. So dependent on the changes you expect to see at the BBB you have to choose your appropriate tracer!

Hi,

We use higher weight Evans Blue (70 KD) and lower weight FITC-dextran in mice using i.v. injections. Further, you may also consider using Sulpho biotin NHS.