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Review
. 2008 Mar;93(2):F153-61.
doi: 10.1136/adc.2006.108837.

Pathogenesis of cerebral white matter injury of prematurity

O Khwaja  1 , J J Volpe
Affiliations
Review

Pathogenesis of cerebral white matter injury of prematurity

O Khwaja et al. Arch Dis Child Fetal Neonatal Ed. 2008 Mar.

Abstract

Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury.

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Figures

Figure 1
Figure 1
Schematic diagram of the three major forms of white matter abnormality in premature infants. Cystic (A) and non-cystic (B) periventricular leukomalacia exhibit the two components of the lesion—that is, focal necrosis deep in the white matter and more diffuse injury characterised by a loss of pre-oligodendrocytes and marked astrogliosis. In cystic disease (A) the focal necrotic lesions are macroscopic and evolve to cysts, whereas in non-cystic disease (B) the focal lesions are microscopic and evolve to glial scars. Diffuse white matter gliosis (DWMG) (without focal necrosis) may represent the mildest form of the spectrum of cerebral white matter injury.
Figure 2
Figure 2
Pathogenetic mechanisms in PVL. See text for details.
Figure 3
Figure 3
Microglia as a convergence point for upstream and downstream mechanisms in pathogenesis. See text for details.
See this image and copyright information in PMC

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