Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury

Figure 1

Schematic of mechanisms of neuroprotective effects of astrocytes. There are at least seven distinct mechanisms by which astrocytes protect neurons from damage. (1) Protection against glutamate toxicity occurs through astrocyte uptake of extracellular glutamate through the excitatory amino acid transporter 2 (EAAT2) and the glutamate transporter 1 (GLT-1). (2) Protection against redox stress through the activation of Nrf2 and regulation of antioxidant genes; protection of the neurons is also advanced by the export of glutathione precursors to help neurons synthesize glutathione. (3) Mediation of mitochondrial repair mechanisms by which astrocytes received damaged mitochondria from neurons for mitophagy and in return deliver healthy mitochondria to the neurons. (4) Protection against glucose-induced metabolic stress, which involves astrocytes taking up extracellular glucose for storage as glycogen; the glycogen can be released to neurons as lactate for their metabolism at a later time. (5) Protection against iron toxicity, in which astrocytes sequester free iron for storage in complex with ferritin. (6) Modulation of the immune response in the brain occurs by astrocyte inhibition of both T cell and monocyte activation; the mechanisms for these actions are not fully known. (7) Maintenance of tissue homeostasis in the presence of DNA damage, where astrocytes can effectively repair their DNA through both homologous recombination and nonhomologous end joining, following pause of the cell cycle.