STUDY OF CEREBRAL ISCHEMIC TOLERANCE : PART 2 : SUPERDELAYED NEURONAL CHANGES DUE TO CHRONIC HYPOPERFUSION IN AGED ANIMALS

脑缺血耐受性研究：第 2 部分：老年动物慢性灌注不足导致的超延迟神经元变化

• 批准号: 07670742
• 负责人: NARITOMI Hiroaki
• 金额: $ 1.34万
• 依托单位: NATIONAL CAROIOVASCULAR CENTER RESEARCH INSTITUTE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670742/
• 关键词: cerebral ischemia; chronic cerebral hypoperfusion; aging; ischemic tolerance; delayd neuronal death; cerebral blood flow; 加齢

In order to elucidate the difference of cerebral tolerance to ischemia between aged and young animals, two experimental studies were performed. In experiment A,Sprague-Dawley rats with 2 months of age (young group) and 18 months of age (aged group) were subjected to right middle cerebral artery occlusion. Neuronal changes in teh ipsilateral thalamus were studied at 3 days, 1 week and 2 weeks after occlsuion, respectively. After occlusion, all the animals developed infarction in the ipsilateral cerebral cortex and the lateral caudoputamen. At 3 days after occlsuion, the thalamus was pared in both groups. At 1 week after occlusion, 40% of young animals showed mild neuronal changes in the ipsilateral thalamus, and 60% of aged animals exhibited mild neronal changes in the thalamus. At 2 weeks after occlusion, all the young and aged animals displayd neuronal changes in the ipsilateral thalamus. The extent of changes were more widely spreaded in aged animlas as compared with young animals. I … More n experiment B,mongolian gerbils with 2 months of age (young group) and 18-20 months of age (aged group) were subjected to the occlusion of right internal carotid artery and left external carotid artery. Both groups were further divided into two subgroups, one for cerebral blood flow measurments and the other for histological examinations. After occlusion, 60% of young animals and 70% of aged animals showed severe cerebral blood flow reduction by more than 50%, and the remainders exhibited moderate blood flow reduction by less than 50%. IN both groups, animals with severe reduction all showed ischemic symptoms and died within 3 days after occlusion, whereas those with moderate redcution revealed no ischemic symptoms. Histological examinations were performed in the non-symptomatic animals at 1 week, 1 month and 3 months after occlsuion, respectively. At 1 week after occlusion, none of animals in young and aged groups exhibited-neuronal changes. At 1 month after occlusion, none of animlas in young group exhibited neuronal changes. However, 3 of 9 animals in aged group developed neuronal changes in the cerebral cortex and/or hippocampus CA1 area. At3 months after occlusion, only 1 of 8 animals in young group showed neuronal changes in the hoppocampus CA1 region. On the other hand, 5 of 8 animals in aged group displayd neuronal changes in teh cerebral cortex and/or hippocampus. The results of teh present study suggest that the ages brain is more vulnerable to ischemic insults as compared with the young brain. Moderate hypoperfusion ensuing for a chronic interval may cause cortical and hippocampal neuronal changes in the aged brain. Less

为了阐明老年和青年动物脑缺血耐受性的差异，进行了两项实验研究。在实验A中，对2月龄（青年组）和18月龄（老年组）的Sprague-Dawley大鼠进行右侧大脑中动脉闭塞。分别于术后3天、1周和2周观察同侧丘脑神经元的变化。闭塞后，所有动物在同侧大脑皮层和外侧尾壳核发生梗死。术后第3天，两组大鼠丘脑均被覆盖。在1周后闭塞，40%的年轻动物表现出轻微的神经元的变化，在同侧丘脑，和60%的老年动物表现出轻微的神经元的变化，在丘脑。阻断后2周，所有青年和老年动物的同侧丘脑均出现神经元改变。老年动物比青年动物的变化范围更广。我 ...更多信息 实验B，选用2月龄（青年组）和18-20月龄（老年组）的蒙古沙土鼠，分别阻断右侧颈内动脉和左侧颈外动脉。两组又分为两个亚组，一组进行脑血流量测定，另一组进行组织学检查。闭塞后，60%的年轻动物和70%的老年动物表现出严重的脑血流量减少超过50%，而闭塞者表现出中度血流量减少小于50%。在两组中，重度缩小的动物均显示缺血症状，并在闭塞后3天内死亡，而中度缩小的动物则无缺血症状。分别于术后1周、1个月和3个月对无症状动物进行组织学检查。缺血后1周，青年组和老年组均无神经元改变。阻断后1个月，幼年组动物无神经元改变。而老龄组9只动物中有3只出现大脑皮质和/或海马CA 1区神经元改变。3个月时，幼年组8只动物中仅有1只出现海马CA 1区神经元改变。老龄组8只中有5只出现大脑皮层和/或海马神经元改变。本研究结果提示老年人的大脑比年轻人的大脑更容易受到缺血性损伤。慢性中度低灌注可引起老年脑皮质和海马神经元的改变。少

项目成果

Nishimura H,Naritomi HH: "In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis." Stroke. 27:6. 1099-1104 (1995)

Nishimura H，Naritomi HH：“颈动脉血栓形成沙鼠模型中抗血小板药物的体内评估。”

Naritomi H,Sanpei K: "Protein synthesis inhibitor prevents delayed neuronal death following middle cerebral artery occlusion in rats." J Cereb Blood Flow Metab. 15:S1. 410 (1995)

Naritomi H、Sanpei K：“蛋白质合成抑制剂可预防大鼠大脑中动脉闭塞后延迟性神经元死亡。”

Naritomi H,Sanpei K.Hirata T,Nishiura M,Gao S,Sawada T: "Protein synthesis inhibitor prevents delayd neuronal death following" J Cereb Blood Flow Metab. 15(S1). 410 (1995)

Naritomi H，Sanpei K.Hirata T，Nishiura M，Gao S，Sawada T：“蛋白质合成抑制剂可预防延迟性神经元死亡”J Cereb Blood Flow Metab。

Nishimura H,Naritomi H,Iwamoto Y,Tachibana H,Sugita M: "In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis" Stroke. 27(6). 1099-1104 (1995)

Nishimura H，Naritomi H，Iwamoto Y，Tachibana H，Sugita M：“颈动脉血栓形成沙鼠模型中抗血小板药物的体内评价”中风。

Naritomi H,Sanpei K: "Protein synthesis inhibitor prevents delayed neuronal death follwoing middle cerebral artery occlusion in rats." J Cereb Blood Flow Metab. 15:Sl. 410- (1995)

Naritomi H，Sanpei K：“蛋白质合成抑制剂可预防大鼠大脑中动脉闭塞后的迟发性神经元死亡。”