Increasing the Permeability of the Blood-brain Barrier in Three Different Models in vivo

Blood-brain barrier (BBB) plays significant roles in the circumstance maintains for the central nervous system (CNS). The dysfunction of the BBB could occur in all pathological conditions of CNS diseases, such as ischemic stroke, cerebral edema, or inflammatory disorders. However, the comparisons among different animal models with a broken BBB in vivo are still need to be further studied.

Here we used three different mice models in vivo, including MCAO induce, LPS treatment, and cold injury to mimic the situation in clinic. The permeability of BBB in three models was detected by perfusion of Evan's blue dye. The functional proteins of the BBB including claudin-5, VE-cadherin, and caveolin-1 were compared in three different models in vivo.

With the hyperpermeability of Evan's blue in the three models, both claudin-5 and VE-cadherin were decreased, while the expression of caveolin-1 was increased. Our study showed that BBB dysfunction induced by MCAO in mice was relatively stable, reliable, and moderate compared with LPS or cold injury-induced BBB permeability models, although the procedural time was generally long and operation complexity was hard. Moreover, our study also found that the model of the increased BBB permeability by cold injury was severe in the regional cerebral tissue and the model treated with LPS was mild in the global cerebral tissue. The operation of the two models in vivo was easy, quick, and stable.

The MCAO model was the most suitable for studying the permeability of BBB among the three models in vivo.