Figure 11.

Monocyte activity at the blood–brain interface. 1, Activated by inflammatory stimuli (e.g., LPS), monocytic cells release proinflammatory cytokines such as TNF. This can occur in the brain or in peripheral tissues. 2, TNF acts on the cerebral microvasculature by inducing the expression of Angpt2, which permits vascular changes that promote the adhesion of CD68⁺GR1⁻ monocytes. 3, 4, When firmly attached, these cells adopt a rod-shaped morphology and crawl on the endothelium. 5, Most frequently at capillary branch points, they can divide into two daughter cells that continue to crawl in opposite directions. 6, While monitoring the environment, they can extend a long cytoplasmic process whose function is unknown. 7, Where needed, some of them cross the blood–brain barrier by a process of diapedesis. 8, 9, After infiltration, they search for a vacant niche in which they ultimately differentiate into perivascular macrophages. Although CD68⁺GR1⁻ monocytes do not give rise to microglia in response to endotoxemia, it remains to be investigated whether they can do so in other inflammatory conditions.