PT  - JOURNAL ARTICLE
AU  - O Khwaja
AU  - J J Volpe
TI  - Pathogenesis of cerebral white matter injury of prematurity
AID  - 10.1136/adc.2006.108837
DP  - 2008 Mar 01
TA  - Archives of Disease in Childhood - Fetal and Neonatal Edition
PG  - F153--F161
VI  - 93
IP  - 2
4099  - http://fn.bmj.com/content/93/2/F153.short
4100  - http://fn.bmj.com/content/93/2/F153.full
SO  - Arch Dis Child Fetal Neonatal Ed2008 Mar 01; 93
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.