TABLE 1.
Effects of selective GR agonists, modulators and inhibitors on brain cells
| Cell type | Influence of agonist (dexamethasone) |
Influence of agonist (methyl-prednisolone) |
Influence of modulator (ginsenoside Rg1) |
Influence of modulator (icariin) |
Influence of antagonist (mifepristone) |
Refs |
|---|---|---|---|---|---|---|
| Glutamatergic neurons | ↓ Glutamate release | ↑ Glutamate signaling | ↓ NLRP inflammasome induced neuronal damage | ↓ Depolarization | [63,65,157,169,170] | |
| ↓ Purkinje cell apoptosis | ||||||
| GABAergic neurons | ↑ GABA release | ↓ GABA signaling | ↓ NLRP inflammasome induced neuronal damage | ↓ GABA response | [64,65,169,171] | |
| ↑ Sensitizes GABA receptors | ↓ Purkinje cell apoptosis | |||||
| Dopaminergic neurons | ↓ Inflammation-induced neuronal degeneration | ↓ LPS-induced neurotoxicity and cell death | [172,173] | |||
| Astrocytes | ↓ Proliferation | ↓ Activation | ↑ Association with vasculature in the ischemic brain | ↑ Proliferation | [69,174,175] | |
| ↓ GR expression | ↓ GFAP and CSPG in activated astrocytes | ↑ GR expression (to normal level) | ||||
| Oligodendrocytes | ↑ Progenitor cell apoptosis | ↓ AMPA-induced cell death | [67,176] | |||
| ↑ MHC II molecules | ||||||
| Microglia | ↓ Microglial activation | ↓ Hypothermic cytotoxicity | ↓ LPS-induced microglial activation | ↓ LPS-induced microglial activation | ↓ Progesterone suppression of immune response involving microglia | [68,69,160,173,174,177,178] |
| ↓ MHC expression | ↓ Interleukin-6 secretion | ↓ LPS-induced prostaglandin secretion | ||||
| Endothelial cells | ↑ Tight-junction proteins | ↓ Adhesion molecule expression | ↑ Vascular endothelial growth factor | ↓ P-glycoprotein expression | [42,51,59,127,146,147] | |
| ↑ P-glycoprotein expression | ↓ Cytochrome P450 enzymes expression | |||||
| Pericytes | ↑ Vascular coverage in neonates | ↓ Glucocorticoid-induced apoptosis | [179] | |||
| ↑ Markers of apoptosis | ||||||
Abbreviations: NLRP nucleotide-binding oligomerization domain-like receptor protein; GABA gamma-aminobutyric acid; LPS lipopolysaccharide; GR glucocorticoid receptor; GFAP glial fibrillary acidic protein; CSPG chondroitin sulfate proteoglycans; MHC major histocompatibility complex; AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.