Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats
Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats
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DOI：
10.2174/156720205774962674
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发表时间：
2005-12-01
影响因子：
2.1
通讯作者：
McKinney, M
中科院分区：
文献类型：
--
作者：
He, Z;Crook, JE;McKinney, M
本研究探讨的假设，老化定义的50%的生存年龄损害缺血预处理（ITC）提供的神经保护。分别对64只4月龄和24月龄的雄性F344大鼠进行IPC（3分钟缺血）或假手术，然后在2天后进行10分钟（完全）缺血或假手术。每个年龄组分为假手术-假手术（SS）组、预处理-假手术（PS）组、预处理-缺血（PI）组和假手术-缺血（SI）组。全脑缺血后8d，观察海马CA 1区N-甲基-D-天冬氨酸受体1（NMDAr 1）和caspase-3活性肽（C3 AP）的表达。老年SI组的CA 1“活细胞比率”大于年轻SI组（32 +/- 6% vs. 17 +/-5%，p < 0.05），而IPC提供的对完全缺血的保护程度在老年人中比年轻人降低（53 +/- 17% vs. 241 +/-25%，P < 0.0001）。NMDAr 1免疫荧光的基础水平在年轻动物中显著更高，而与相应的年轻组相比，在所有三个老年缺血组中C3 AP阳性细胞的数量更大（p < 0.01，p=0.055和p < 0.05）。使用Fluoro Jade C标记的退化神经元评估细胞损伤的第四种方法也是强烈嗜酸性的。青年SI组FluoroJadeC阳性细胞数高于老年SI组（P < 0.05），提示缺血性细胞死亡机制可能随增龄而改变。总之，衰老改变了CA 1神经元缺血性细胞死亡的机制，缺血耐受机制也因衰老而减弱。
The present study examines the hypothesis that aging defined by the 50% survival age compromises neuroprotection afforded by ischemic preconditioning (ITC). Sixty-four male F344 rats aged 4- and 24-months, respectively, were subjected to IPC, (3-min ischemia) or sham-surgery followed by 10-min (full) ischemia or sham-surgery 2 days later. There were 4 groups at each age: sham-surgery-sham-surgery (SS), preconditioning-sham-surgery (PS), preconditioning-ischemia (PI) and sham-surgery-ischemia (SI) groups. Assessments of histology and immunoreactivities of N-methyl-Daspartic acid receptor 1 (NMDAr1) and caspase-3 active peptide (C3AP) in the hippocampal CA1 region were performed 8 days after full ischemia. The CA1 "living cell ratio" was greater in the aged SI group than in the young SI group (32 +/- 6% vs. 17 +/- 5%, p < 0.05), whereas the degree of protection against full ischemia afforded by IPC was reduced in the aged compared with the young (53 +/- 17% vs. 241 +/- 25%, P < 0.0001). The basal level of NMDAr1 immunofluorescence was significantly higher in young animals, while the numbers of C3AP-positive cells were greater in all three aged ischemic groups as compared to respective young groups (p < 0.01, p=0.055 and p < 0.05). A fourth method of assessing cell damage using Fluoro Jade C labeled degenerating neurons that were also intensively eosinophilic. Counts of Fluoro Jade C-positive cells were higher in the young SI group than in the aged SI group (P < 0.05), suggesting that mechanisms of ischemic cell death may change with aging. In conclusion, aging alters mechanisms of ischemic cell death in CA1 neurons and ischemic tolerance mechanisms are blunted by aging.