RT Journal Article
SR Electronic
T1 Pathogenesis of cerebral white matter injury of prematurity
JF Archives of Disease in Childhood - Fetal and Neonatal Edition
JO Arch Dis Child Fetal Neonatal Ed
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP F153
OP F161
DO 10.1136/adc.2006.108837
VO 93
IS 2
A1 O Khwaja
A1 J J Volpe
YR 2008
UL http://fn.bmj.com/content/93/2/F153.abstract
AB 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.