FIGURE 10.

Blood-brain barrier breakdown and dysfunction in multiple sclerosis. Hallmark features of multiple sclerosis (MS) include vascular dysfunction, neuroinflammation, and oligodendrocyte degeneration causing neuronal demyelination and loss. An early blood-brain barrier (BBB) breakdown, neurotoxic fibrin(ogen) accumulation, reduced tight junction (TJ) protein expression, and endothelial degeneration are features of both human MS and animal MS models. Leukocytes infiltrate across the BBB in a multistep sequential process involving capture, rolling, activation, adhesion, crawling, and trans- or paracellular diapedesis. This process requires crosstalk between leukocytes and endothelial cells via precise molecular interactions, as illustrated in the diagram. See the main text for details. MMPs, matrix metalloproteinases; RBC, red blood cell.