TY - JOUR 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 SP - F153 LP - F161 DO - 10.1136/adc.2006.108837 VL - 93 IS - 2 AU - O Khwaja AU - J J Volpe Y1 - 2008/03/01 UR - http://fn.bmj.com/content/93/2/F153.abstract N2 - 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. ER -