EFFECT OF AGE IN RODENT MODELS OF FOCAL AND FOREBRAIN ISCHEMIA

Background and Purpose The majority of animal experiments examining th e nature and treatment of stroke have used relatively young animals ra nging in age from 2 to 6 months. However, significant morphological, n eurochemical, and behavioral changes occur with aging in rodents, part icularly during the first 24 months of age. This study examines the ef fect of age in two models of transient ischemia, a forebrain and a foc al model, in male Wistar rats. Methods We induced forebrain ischemia o f 12 minutes' duration by bilateral carotid artery occlusion with cont rolled 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 H g. Physiological parameters were monitored and maintained within norma l limits. On day 7 after ischemia, the rats were perfusion-fixed and t he brains removed for quantitative histopathology. Results After foreb rain ischemia, older rats showed significantly less CA1 neuronal necro sis than the younger group (P<.003), whereas both striatal and neocort ical injury were significantly greater in the older group (P<.05). Amo ng animals subjected to focal ischemia, the volume of infarcted tissue and the number of necrotic neurons in the area adjacent to the infarc tion were both greater in older rats (P<.05). Conclusions This study e mphasizes the importance of age in models of forebrain and focal ische mia. The interaction between age-related changes in morphology, neuroc hemistry, and behavior on the ischemic cascade complicates the interpr etation of mechanistic data; and pharmacological effects observed in y ounger animals may not necessarily translate to an older population.