Transient global brain ischemia in young and aged rats: differences in severity and progression, but not localisation, of lesions evaluated by magnetic resonance imaging.

A model of transient global brain ischemia consisting of bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O2-85% N2) for 20 min was studied by means of MRI in young and aged Fischer 344 rats (3-4 and 24-26 months, respectively). Ischemia was assessed by full suppression of spontaneous EEG activity, which reappeared and normalized similarly in the two age-groups. The survival of young with respect to aged rats was considerably higher both at 24 h (20/20, i.e. 100% vs 12/16, i.e. 75%) and at 48 h (16/20, i.e. 80% vs 6/16, i.e. 38%). The localisation of brain lesions, their severity and progression were evaluated by a diffusion-weighted MRI (DWI) sequence at 24 and 48 h post-ischemia. There were no DWI-detectable lesions in eight out of 20 young and two out of 12 aged rats. The localisation of DWI-detected lesions was rather similar in rats of the two age-groups. In fact, the cerebral cortex, mainly parietal, occipital and temporal lobes were damaged in 83% of young and 90% of aged rats. The respective percentages for the thalamus were 83 and 60%, for the striatum 58 and 50%, and for the hippocampus 25 and 30%. The lesions present in the cerebral cortex and the thalamus were considerably more severe in aged than in young rats. In conclusion, in spite of similar localisation of ischemic lesions in the two age-groups, their incidence was higher, appearance more rapid and severity more pronounced in aged with respect to young rats. This resulted in a considerably higher mortality of the former. The overall data indicate that the age issue is very important in experimental ischemia research.