Transient ADC change precedes persistent neuronal death in hypoxic–ischemic model in immature rats

A brief ischemia causes delayed neuronal death (DND) in some areas vulnerable to ischemia. Additionally, it causes a transient reduction in the apparent diffusion coefficients (ADCs) obtained from diffusion-weighted magnetic resonance imaging (DWI), which is a powerful tool to detect ischemic changes in the brain at a very early stage. The present study examined long-term histopathological changes in the hippocampal neurons up to 30 days after a very mild hypoxic–ischemic (HI) insult in immature rats. Three-week-old male rats were subjected to 15- and 30-min HI insults (15-min HI and 30-min HI) and serial DWI was performed. Only animals whose ADC reduction pattern was transient were examined histopathologically. ADCs decreased significantly during the insult, and the ADC values of 30-min HI group were significantly lower than those of 15-min HI group. Ischemic neuronal changes were observed up to 30 days after the insult in 30-min HI group, although ADCs in the chronic stage were within the normal range. In addition, neuron density in 30-min HI group was significantly lower in the chronic stage (on days 14 and 30) than in 15-min HI group. A very mild hypoxia–ischemia followed by a transient ADC reduction causes persistent neuronal death, which can be predicted by measuring ADCs during the acute insult.