The changing phenotype of microglia from homeostasis to disease

Luo, Xiao-Guang; Chen, Sheng-Di

As an active sensor in the brain, microglia respond to even minor stimuli; however, different types of stimulation may also lead to different actions of microglia and thus be either harmful or beneficial to neuronal survival. In a neonatal mouse MPTP-induced brain injury model, microglia activated by systemic administration of LPS were shown to be neuroprotective. In contrast to the MPTP model, LPS-activated microglia in neonatal mice receiving a stereotaxic injection of ethanol into the striatum were shown to be neurotoxic, and systemic LPS administration in the ethanol-injury model caused a marked increase both in the volume of necrotic lesions and in the number of degenerating neurons in the striatum [168] . Even with the same stimuli, the degree can also determine microglial release of toxic versus protective effectors [169] ; neurotoxic cytokines and ROS were released from microglia only in response to mild neuronal injuries, while trophic microglial effectors such as BDNF and GDNF were up-regulated in response to all degrees of neuronal injury [169] . Additionally, different types of pain resulted in differing activations of microglia [170] .