Pathophysiology of glia in perinatal white matter injury
Article first published online: 31 MAR 2014
Copyright © 2014 Wiley Periodicals, Inc.
How to Cite
Back, S. A. and Rosenberg, P. A. (2014), Pathophysiology of glia in perinatal white matter injury. Glia. doi: 10.1002/glia.22658
- Article first published online: 31 MAR 2014
- Manuscript Accepted: 27 FEB 2014
- Manuscript Revised: 13 FEB 2014
- National Institutes of Neurological Diseases and Stroke (NIH) . Grant Number: 1R01NS054044 and R37NS045737
- National Institute of Aging (NIH) . Grant Number: 1R01AG031892-01
- American Heart Association . Grant Number: 11GRNT7510072
- March of Dimes Birth Defects Foundation . Grant Number: # 6-FY11-323
- NIH . Grant Numbers: P30 HD018655 and R01 NS066019 , Whitehall Foundation and Baby Alex Foundation.
Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbances and maternal–fetal infection. During the acute phase of WMI, pronounced oxidative damage occurs that targets late oligodendrocyte progenitors (pre-OLs). The developmental predilection for WMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible pre-OLs that are vulnerable to a variety of chemical mediators including reactive oxygen species, glutamate, cytokines, and adenosine. During the chronic phase of WMI, the white matter displays abberant regeneration and repair responses. Early OL progenitors respond to WMI with a rapid robust proliferative response that results in a several fold regeneration of pre-OLs that fail to terminally differentiate along their normal developmental time course. Pre-OL maturation arrest appears to be related in part to inhibitory factors that derive from reactive astrocytes in chronic lesions. Recent high field magnetic resonance imaging (MRI) data support that three distinct forms of chronic WMI exist, each of which displays unique MRI and histopathological features. These findings suggest the possibility that therapies directed at myelin regeneration and repair could be initiated early after WMI and monitored over time. These new mechanisms of acute and chronic WMI provide access to a variety of new strategies to prevent or promote repair of WMI in premature infants. GLIA 2014