Pathophysiology of periventricular leukomalacia:what we learned from animal models

Periventricular leukomalacia （PVL）, a white matter injury （WMI） affecting the premature infant＇s brain is commonly associated with ce- rebral palsy （CP）. Among premature infants 〈 1,500 g, approximately 7,000 develop CP yearly and 20,000-30,000 exhibit major cognitive deficits yearly （Volpe, 2009）. PVL results from hypoxia-ischemia （HI） with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. Risk factors for the development of PVL include： prematurity associated with immature cerebrovascular development, HI insults with lack of appropriate auto-regulation of cerebral blood flow, free radical production, energy deprivation, intrauterine infec- tion and chorioamnionitis. Affected infants show definitive signs of cerebral palsy such as spastic diplegia, seizures, developmental delay, visual and hearing impairment, scoliosis and incontinence by 6-9 months of age. PVL can also occur in term infants with certain con- genital cyanotic heart disease which will not be our focus here （Volpe, 2001）.