Glutamate-mediated glial injury: mechanisms and clinical importance

Glia. 2006 Jan 15;53(2):212-24. doi: 10.1002/glia.20275.


Primary and/or secondary glial cell death can cause and/or aggravate human diseases of the central nervous system (CNS). Like neurons, glial cells are vulnerable to glutamate insults. Astrocytes, microglia, and oligodendrocytes express a wide variety of glutamate receptors and transporters that mediate many of the deleterious effects of glutamate. Astrocytes are responsible for most glutamate uptake in synaptic and nonsynaptic areas and consequently, are the major regulators of glutamate homeostasis. Microglia in turn may secrete cytokines, which can impair glutamate uptake and reduce the expression of glutamate transporters. Finally, oligodendrocytes, the myelinating cells of the CNS, are very sensitive to excessive glutamate signaling, which can lead to the apoptosis or necrosis of these cells. This review aims at summarizing the mechanisms leading to glial cell death as a consequence of alterations in glutamate signaling, and their clinical relevance. A thorough understanding of these events will undoubtedly lead to better therapeutic strategies to treat CNS diseases affecting glia and in particular, those that involve damage to white matter tracts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Brain Injuries / pathology
  • Brain Ischemia / pathology
  • Glutamic Acid / physiology*
  • Humans
  • Multiple Sclerosis / pathology
  • Nervous System Diseases / pathology*
  • Neurodegenerative Diseases / pathology
  • Neuroglia / physiology*
  • Receptors, Glutamate / physiology
  • Signal Transduction / physiology


  • Amino Acid Transport System X-AG
  • Receptors, Glutamate
  • Glutamic Acid