Effect of age in rodent models of focal and forebrain ischemia

Background and Purpose The majority of animal experiments examining the nature and treatment of stroke have used relatively young animals ranging in age from 2 to 6 months. However, significant morphological, neurochemical, and behavioral changes occur with aging in rodents, particularly during the first 24 months of age. This study examines the effect of age in two models of transient ischemia, a forebrain and a focal model, in male Wistar rats. Methods We induced forebrain ischemia of 12 minutes' duration by bilateral carotid artery occlusion with controlled hypotension at a mean blood pressure of 45 mm Hg and, using an intraluminal filament technique, induced focal middle cerebral artery occlusion of 100 minutes' duration at a mean blood pressure of 60 mm Hg. Physiological parameters were monitored and maintained within normal limits. On day 7 after ischemia, the rats were perfusion-fixed and the brains removed for quantitative histopathology. Results After forebrain ischemia, older rats showed significantly less CA1 neuronal necrosis than the younger group (P<.003), whereas both striatal and neocortical injury were significantly greater in the older group (P<.05). Among animals subjected to focal ischemia, the volume of infarcted tissue and the number of necrotic neurons in the area adjacent to the infarction were both greater in older rats (P<.05). Conclusions This study emphasizes the importance of age in models of forebrain and focal ischemia. The interaction between age-related changes in morphology, neurochemistry, and behavior on the ischemic cascade complicates the interpretation of mechanistic data; and pharmacological effects observed in younger animals may not necessarily translate to an older population.