gms | German Medical Science

In stroke, the role of the blood-brain barrier (BBB) is unknown. The barrier-forming endothelium paracellularly sealed by tight junctions (TJs) protects the homeostasis of the brain against peripheral disturbances and ensures appropriate metabolite exchange. Sealing of the barrier is caused by claudins (Cldns). Among them the function of Cldn3 is completely unclear.

Cldn3 deficient mice were analysed for BBB permeability (small/large molecules), expression (mRNA, protein amounts) and morphology (electron/immune-microroscopy) of the TJs in vitro after hypoxia and in vivo after middle cerebral artery occlusion (MCAO; staining/quantification of stroke/odema).

We found:

1.

Cldn3 tightened the BBB for small molecules, limited endothelial endocytosis of proteins, contributed to TJ-formation, and prevented inflammatory processes.

2.

After acute hypoxia of isolated mouse brain capillaries, the BBB specific TJ marker Cldn5 remained unaffected in the presence of Cldn3; in Cldn3 deficiency, Cldn5 drastically declined at the TJs.

3.

In the postischemic infarction process after MCAO in mice, Cldn3 accounted for an increased infarct volume due to increased swelling of the affected brain.

Collectively, Cldn3 contributes to the intactness of the BBB under physiological and pathological conditions, but preserves the stroke region as Cldn3, at the BBB, prevents detumescence of the injured area. Thus, modulation of BBB tightening Cldns might help to improve stroke treatment.