A simplified schematic illustration of the interaction between the trios of neurons, astrocytes, and microglia in the CNS under the normal (a) and pathological conditions (b). Healthy neurons are able to tightly regulate the activation of their neighboring glial cells. Meanwhile both astrocytes and microglia help maintain the neuronal activity. Under various diseased conditions, this homeostasis is broken so that neurons lose their controlling ability but instead deliver damage signals to glial cells, which in turn may exacerbate neuronal damage through inflammation. The cross-talk among astrocytes and microglia themselves and its aftermath on neurons is currently not very clear.