Fig. 3

The process of immune cell migration across the blood–brain barrier (BBB) can be delineated as a series of consecutive stages. a Rolling. Immune cells engage with the endothelium through the interaction between PSGL-1 and P-selectin in the inflamed endothelial cells. b Arrest. The immune cells are activated upon transient contact with the endothelium, resulting in their firm adhesion to the endothelium. c Crawling. The immune cells polarize and crawl to locate permissive sites. d Diapedesis. The ultimate step is in which the immune cells traverse the barrier through either a paracellular (across the tight junctions) or transcellular pathway. This figure is a modification of Fig. 4 by Mastorakos et al. [6]. CXCL12 C-X-C motif chemokine ligand 12, CXCR4 chemokine (C-X-C motif) receptor 4, ICAM intracellular adhesion molecule, IL-1β interleukin-1β, LFA lymphocyte function-associated antigen, PSGL-1 P-selectin glycoprotein ligand-1, TNF-α tumor necrosis factor-α, VCAM vascular cell adhesion molecule, VLA very late antigen