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BACKGROUND: To date, animal models of white matter damage remain controversial. Mild grey matter damage should be the basis for animal models to investigate white matter disease.OBJECTIVE: To establish white matter damage in neonatal rats and evaluate feasibility of the established model by observing myelination and synaptic ultrastructure.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Histology and Embryology of Guangzhou Medical College from December 2008 to May 2009.MATERIALS: H600 transmission electron microscopy was provided by Hitachi, Japan.METHODS: A total of 39 neonatal, Sprague Dawley rats were randomly assigned to normal control (n = 12), sham-surgery (n = 12), and white matter damage (n = 15) groups. White matter damage rats were subjected to right common carotid artery ligation, followed by inhalation of nitrogen oxygen gas mixture (6% oxygen) for 4 hours. MAIN OUTCOME MEASURES: Myelin sheath and synaptic ultrastructure in the injured (right) hippocampal CA1 region in 1-month-old rats were observed through the use of transmission electron microscopy, and pathological changes in the cerebral cortex and corpus callosum of the right hemisphere were detected by hematoxylin-eosin staining. RESULTS: Obvious tissue loss was observed in the corpus callosum of the injured (right) hemisphere. Injured oligodendrocytes and disrupted myelination were observed in the white matter damage group. However, synaptic length in the active zones, width of synaptic cleft, thickness of postsynaptic density, and curvature of the synaptic interface remained unchanged following injury, compared with the control and sham-surgery groups (P > 0.05).CONCLUSION: The established white matter damage model resulted in changes in myelination and slightly altered synaptic ultrastructures. The model could function as an ideal model for white matter damage in neonatal rats.