Demyelination as a rational therapeutic target for ischemic or traumatic brain injury

Exp Neurol. 2015 Oct:272:17-25. doi: 10.1016/j.expneurol.2015.03.017. Epub 2015 Mar 24.

Abstract

Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients.

Keywords: Cerebral ischemia; Demyelination; Oligodendrocyte; Remyelination; Traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Axons / pathology
  • Brain Injuries / complications*
  • Brain Injuries / therapy*
  • Cell Death
  • Cognition Disorders / etiology
  • Cytokines / metabolism
  • Demyelinating Diseases / complications
  • Demyelinating Diseases / etiology*
  • Humans
  • Ischemia / complications*
  • Ischemia / therapy*
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Oligodendroglia / pathology

Substances

  • Cytokines