Figure 1.

Differences in microglial activation in response to vascular injury in normal and diabetic mice. A, Cerebral microbleeds trigger ATP release in brain parenchyma, resulting in the activation of microglial P2Y12 receptors. The M2-like microglia migrate to the injured vessel and repair the lesion. B, In diabetic/hyperglycemic mice, IFN-γ triggers a shift in microglia to a proinflammatory M1-like phenotype, which expresses lower levels of P2Y12R. Thus, microglial cells are no longer able to repair vascular lesions; this leads to secondary vascular leakage. These events might increase the risk of the development of dementia later in life. C, Blocking IFN-γ signaling restores P2Y12R expression levels, M2-like microglial response, and vascular repair. This approach might also decrease the risk of vascular dementia and Alzheimer's disease.