A new model of white matter injury in neonatal rats with bilateral carotidartery occlusion

Periventricular leukomalacia is an important cause of cerebral palsy and ch aracterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neo natal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had whit e matter changes including coagulation necrosis and cystic lesions in and a round the internal capsule, while only two had small cerebral infarction an d five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matt er in the animals with bilateral carotid artery occlusion (BCAO). Amyloid p recursor protein (APP) immunohistochemistry demonstrated various APP-immuno reactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is mo re vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal bra in, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was a lso indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain. (C) 1999 Elsevier Science B.V. All rights reserved.