OBJECT: More than 100 clinical trials based on animal models have failed to identify a clinically effective neuroprotectant for stroke. Current models of stroke do not account adequately for aging nor do they incorporate the use of female animals. The authors evaluated the pathological and physiological differences in stroke in young, adult, and elderly female rats. METHODS: Three groups of female Sprague-Dawley rats were studied. Nine rats were divided into three groups: young (3 months); adult (9 months); and elderly (18 months). Intraluminal filament occlusion was performed for 120 minutes while cerebral blood flow was monitored. Physiological parameters were assessed. Infarction volumes were quantified at 24 hours. The mean arterial pressure increased in the young animals (103 +/- 3.51 mm Hg; p < 0.001) during occlusion and decreased in the elderly group (65.56 +/- 3.03 mm Hg; p < 0.01). Cortical and striatal infarction volumes in the elderly animals were substantially larger (p < 0.05). Young animals exhibited a lesser decrement in cerebral blood flow (p < 0.05) during ischemia. CONCLUSIONS: This study reinforces the importance of using older animals for the researching and treatment of stroke. Elderly animals show differences in response mechanisms, ischemic consequences, and histological changes. These differences may partially explain the current lack of success involved in using young-animal models to predict the clinical efficacy of neuroprotective agents.
OBJECT: More than 100 clinical trials based on animal models have failed to identify a clinically effective neuroprotectant for stroke. Current models of stroke do not account adequately for aging nor do they incorporate the use of female animals. The authors evaluated the pathological and physiological differences in stroke in young, adult, and elderly female rats. METHODS: Three groups of female Sprague-Dawley rats were studied. Nine rats were divided into three groups: young (3 months); adult (9 months); and elderly (18 months). Intraluminal filament occlusion was performed for 120 minutes while cerebral blood flow was monitored. Physiological parameters were assessed. Infarction volumes were quantified at 24 hours. The mean arterial pressure increased in the young animals (103 +/- 3.51 mm Hg; p < 0.001) during occlusion and decreased in the elderly group (65.56 +/- 3.03 mm Hg; p < 0.01). Cortical and striatal infarction volumes in the elderly animals were substantially larger (p < 0.05). Young animals exhibited a lesser decrement in cerebral blood flow (p < 0.05) during ischemia. CONCLUSIONS: This study reinforces the importance of using older animals for the researching and treatment of stroke. Elderly animals show differences in response mechanisms, ischemic consequences, and histological changes. These differences may partially explain the current lack of success involved in using young-animal models to predict the clinical efficacy of neuroprotective agents.
Authors: Zhenjun Tan; Ryan C Turner; Rachel L Leon; Xinlan Li; Jarin Hongpaisan; Wen Zheng; Aric F Logsdon; Zachary J Naser; Daniel L Alkon; Charles L Rosen; Jason D Huber Journal: Stroke Date: 2013-10-30 Impact factor: 7.914