Fig. 11

Diagram showing that severe peripheral inflammation increases CCR5 expression in inflammatory cells, including astrocytes, microglia, and monocytes, by elevating the level of CCL5 in the brain and circulating blood. Overexpression of CCR5 accelerates JAK2 phosphorylation and subsequently promotes pSTAT3 production and nuclear transport to facilitate MMP9 secretion. The increase in MMP9 protein expression decreases the expression of tight junction proteins such as ZO-1 and CLDN5, causing loss of BBB integrity. MVC can partly reverse these impairments by specifically inhibiting CCR5 expression, and CRISPR-mediated JAK2 knockdown exerts identical effects by impeding the phosphorylation of downstream proteins. Conversely, rCCL5 disrupts BBB integrity via the specific activation of CCR5