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衰老和长春胺衍生物对毛细血管周围微环境的影响:脑毛细血管网络的体视学特征

Effects of aging and vincamine derivatives on pericapillary microenvironment: stereological characterization of the cerebral capillary network.

作者信息

Jucker M, Bättig K, Meier-Ruge W

机构信息

Department of Pathology, University of Basel Medical School, Switzerland.

出版信息

Neurobiol Aging. 1990 Jan-Feb;11(1):39-46. doi: 10.1016/0197-4580(90)90060-d.

DOI:10.1016/0197-4580(90)90060-d
PMID:2325815
Abstract

Changes in the pericapillary microenvironment of adult (18-month-old) and senescent (27 1/2-month-old) Fischer-344 rats treated for 6 weeks with daily IP injections of brovincamine or apovincamine (0, 2.5, 5, 10 mg/kg) were correlated with spontaneous locomotor activity and [14C]-2-deoxyglucose uptake of the brain. The animals were tested for spontaneous locomotor activity in a tunnel maze. Twenty-four hr after behavioral testing and subsequently after a [14C]-2-deoxyglucose injection, brains were removed and capillaries stained with alkaline phosphatase reaction, being later measured with an optical-electronic image analysis technique. Results revealed an increase in intercapillary distance, as a sensitive parameter for capillary density, in the hippocampus (CA1) and in the parietal cortex (area 39) in association with aging. Capillary diameter in the parietal cortex was found to be increased age dependently. A similar age-related increase was also observed in the CA1 field but this age trend was not significant. Chronic treatment with the vincamines produced a dose-dependent reduction in intercapillary distance in senescent animals which approached the level of untreated adult control rats. Significant negative correlations were found between maze locomotion and intercapillary distance among senescent rats. Furthermore, intercapillary distance and local relative 2-deoxyglucose uptake tended to be negatively correlated in both age groups. These findings provide evidence for the working hypothesis that mean intercapillary distance can be considered as an indicator of neuronal activity in the pericapillary microenvironment.

摘要

成年(18个月大)和衰老(27.5个月大)的Fischer-344大鼠每日腹腔注射溴长春胺或阿朴长春胺(0、2.5、5、10mg/kg),持续6周,其毛细血管周围微环境的变化与自发运动活动及大脑的[14C]-2-脱氧葡萄糖摄取相关。在隧道迷宫中测试动物的自发运动活动。行为测试后24小时,随后在注射[14C]-2-脱氧葡萄糖后,取出大脑,用碱性磷酸酶反应对毛细血管进行染色,随后用光电图像分析技术进行测量。结果显示,随着衰老,海马体(CA1)和顶叶皮质(39区)的毛细血管间距增加,这是毛细血管密度的一个敏感参数。发现顶叶皮质的毛细血管直径随年龄增长而增加。在CA1区也观察到类似的与年龄相关的增加,但这种年龄趋势不显著。用长春胺进行慢性治疗可使衰老动物的毛细血管间距呈剂量依赖性降低,接近未治疗的成年对照大鼠的水平。在衰老大鼠中,迷宫运动与毛细血管间距之间存在显著的负相关。此外,在两个年龄组中,毛细血管间距与局部相对2-脱氧葡萄糖摄取均呈负相关。这些发现为以下工作假设提供了证据:平均毛细血管间距可被视为毛细血管周围微环境中神经元活动的一个指标。

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[Effects of vincamine on the mesenteric circulation in the rat. Microcirculatory evaluation of the vasodilator activity of vincamine].
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