Oligodendrocyte pathophysiology and treatment strategies in cerebral ischemia

CNS Neurosci Ther. 2014 Jul;20(7):603-12. doi: 10.1111/cns.12263. Epub 2014 Apr 7.


Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, form a functional unit with axons and play a crucial role in axonal integrity. An episode of hypoxia-ischemia causes rapid and severe damage to these particularly vulnerable cells via multiple pathways such as overactivation of glutamate and ATP receptors, oxidative stress, and disruption of mitochondrial function. The cardinal effect of OL pathology is demyelination and dysmyelination, and this has profound effects on axonal function, transport, structure, metabolism, and survival. The OL is a primary target of ischemia in adult-onset stroke and especially in periventricular leukomalacia and should be considered as a primary therapeutic target in these conditions. More emphasis is needed on therapeutic strategies that target OLs, myelin, and their receptors, as these have the potential to significantly attenuate white matter injury and to establish functional recovery of white matter after stroke. In this review, we will summarize recent progress on the role of OLs in white matter ischemic injury and the current and emerging principles that form the basis for protective strategies against OL death.

Keywords: Excitotoxicity; Hypoxia-ischemia; Oligodendrocyte; Oxidative stress; White matter.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Glutamic Acid / metabolism
  • Humans
  • Oligodendroglia / drug effects
  • Oligodendroglia / pathology*
  • Oligodendroglia / physiology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Treatment Outcome


  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • Adenosine Triphosphate