Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains

Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains
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DOI:
10.1161/01.str.31.11.2707
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发表时间:
2000-11-01
期刊:
影响因子:
8.3
通讯作者:
Hsu, CY
Hsu, CY
中科院分区:
医学1区
文献类型:
--
作者:
Majid, A;He, YY;Hsu, CY

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背景和目的-基因工程小鼠被用于研究脑缺血中单个基因的作用,但是神经元易损性的固有的、应变依赖性差异可能影响实验终点。为了研究这种可能性,局灶性缺血及其与脑血流动力学的关系造成的组织损伤,在3个常见的突变小鼠strains. Methods永久大脑中动脉结扎进行雄性C57 BL/6 J,Balb/C,和129 X1/SvJ小鼠。平均动脉血压,血气,基础和postisemic皮质血流量([C-14]碘安替比林放射自显影和激光多普勒血流仪),后交通动脉通畅性,和梗死面积determined.Results-Basal皮质血流量没有不同的菌株。大脑中动脉结扎后10分钟,缺血皮质中的相对红细胞流量为缺血前流量的6%至7%。尽管血流动力学相似,但Balb/C小鼠的皮质梗死比129 X1/SvJ和C57 BL/6 J小鼠大3倍;后2种品系的梗死面积无显著差异。Balb/C和C57 BL/6 J小鼠的后交通动脉发育不良或缺失率> 90%,而129 X1/SvJ小鼠的后交通动脉发育不良或缺失率< 50%。后交通动脉的存在和通畅性,虽然各菌株之间的变量,不影响缺血前或缺血后皮质血流或承担任何关系缺血性损伤。因此,内在因素,而不是血流动力学的变异性,可能有助于缺血脆弱性的菌株之间的差异。这些发现强调了选择遗传匹配的野生型对照的重要性。
Background and Purpose-Genetically engineered mice are used to study the role of single genes in cerebral ischemia, but inherent, strain-dependent differences in neuronal vulnerability may affect experimental end points. To examine this possibility, tissue injury resulting from focal ischemia and its relationship to cerebral hemodynamics;Were determined in 3 common mutant mouse strains.Methods-Permanent middle cerebral artery ligation was performed in male C57BL/6J, Balb/C, and 129X1/SvJ mice. Mean arterial blood pressure, blood gases, basal and postischemic cortical blood flow ([C-14]iodoantipyrine autoradiography and laser-Doppler flowmetry), posterior communicating artery patency, and infarct size were determined.Results-Basal cortical blood flow did not differ among strains. Ten minutes after middle cerebral artery ligation, relative red cell flow in the ischemic cortex was 6% to 7% of preischemic flow in every strain. Despite similar hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than those in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains was not significantly different. The posterior communicating artery was either poorly developed or absent in > 90% of the Balb/C and C57BL/6J but in < 50% of the 129X1/SvJ mice.Conclusions-The extent of ischemic injury differed markedly between the 3 strains. The presence and patency of posterior communicating arteries, although variable among strains, did not affect preischemic or postischemic cortical blood flow or bear any relationship to ischemic injury. Therefore, intrinsic factors, other than hemodynamic variability, may contribute to the differences in ischemic vulnerability among strains. These findings underscore the importance of selecting genetically matched wild-type controls.