Glucocorticoid signaling in myeloid cells worsens acute CNS injury and inflammation.

Glucocorticoid stress hormones (GCs) are well known for being anti-inflammatory, but some reports suggest that GCs can also augment aspects of inflammation during acute brain injury. Because the GC receptor (GR) is ubiquitously expressed throughout the brain, it is difficult to know which cell types might mediate these unusual "proinflammatory" GC actions. We examined this with cell type-specific deletion or overexpression of GR in mice experiencing seizure or ischemia. Counter to their classical anti-inflammatory actions, GR signaling in myeloid cells increased Iba-1 and CD68 staining as well as nuclear p65 levels in the injured tissue. GCs also reduced levels of occludin, claudin 5, and caveolin 1, proteins central to blood-brain-barrier integrity; these effects required GR in endothelial cells. Finally, GCs compromised neuron survival, an effect mediated by GR in myeloid and endothelial cells to a greater extent than by neuronal GR.