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首页> 外文期刊>Cerebrovascular diseases >Which Aspects of Stroke Do Animal Models Capture? A Multitracer Micro-PET Study of Focal Ischemia with Endothelin-1
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Which Aspects of Stroke Do Animal Models Capture? A Multitracer Micro-PET Study of Focal Ischemia with Endothelin-1

机译：动物模型可以捕捉哪些中风？内皮素-1对局灶性缺血的多示踪Micro-PET研究

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Background: Cortical injections of the vasoconstrictor endothelin-1 (ET1) have widely been used to induce focal circumscribed ischemic lesions in the motor cortex of rodents in the context of stroke recovery studies. In order to apply this model correctly, it is essential to understand the time course of regional flow changes and of the development of penumbra and infarction. Methods: Multitracer micro-PET of ET1 focal ischemia in rats was performed using [C-11]-flumazenil ([C-11]FMZ) as a flow-and viability tracer and [F-18]-fluoromisonidazole ([F-18]FMISO) as hypoxia marker in order to characterize the physiological time-course of this model. Nine adult Sprague-Dawley rats received stereotaxic injections of ET1 into the right primary motor cortex, 3 served as controls. PET imaging was started 2, 3 and 20 h after the last ET1 injection. Histology was obtained at the end of the scans. Standardized uptake value ratios reflecting cerebral blood flow (CBF), [C-11]FMZ-binding and [F-18]FMISO-retention were calculated for the region of hypoperfusion and the normoperfused cortex. Results: CBF in the hypoperfused cortex was significantly reduced (p < 0.01) at 5 h (0.58 +/- 0.025), 6 h (0.54 +/- 0.043) and 23 h (0.66 +/- 0.024) compared to controls (1.00 +/- 0.011) and moderately reduced (p < 0.05) in the remainder of the affected hemisphere at 5 h (0.93 +/- 0.036). [C-11] FMZ-binding was within the control range at all time points. Significant [F-18] FMISO-retention (1.16 +/- 0.091, p < 0.05) was observed only after 6 h in the ischemic core that later turned into infarct. Conclusion: ET1 injections yield reproducible, slowly developing ischemic lesions with constant levels of hypoperfusion. This multitracer micro-PET study suggests that the ET1 model is appropriate for inducing chronic circumscribed ischemic lesions but seems to be less suited for studying acute stroke pathophysiology. (C) 2016 S. Karger AG, Basel
机译：背景：在中风恢复研究的背景下，皮层注射血管收缩素1（ET1）已被广泛用于诱导啮齿类动物运动皮层局灶性局限性缺血性病变。为了正确地应用该模型，必须了解区域流量变化以及半影和梗塞发展的时间过程。方法：使用[C-11]-氟马西尼（[C-11] FMZ）作为流动性和生存力示踪剂，并使用[F-18]-氟亚甲基咪唑（[F-18 [FMISO]作为缺氧标记物，以表征该模型的生理时程。 9只成年Sprague-Dawley大鼠接受立体定向注射ET1到右原发性运动皮层，其中3只作为对照组。在最后一次ET1注射后2、3和20小时开始PET成像。在扫描结束时获得组织学。计算低灌注区域和正常灌注皮质区域的标准化摄取值比率，该比率反映脑血流量（CBF），[C-11] FMZ结合和[F-18] FMISO保留。结果：与对照组（1.00）相比，在5 h（0.58 +/- 0.025），6 h（0.54 +/- 0.043）和23 h（0.66 +/- 0.024）时，灌注不足皮质的CBF显着降低（p <0.01）。 +/- 0.011），并在5h内受影响的半球其余部位适度降低（p <0.05）（0.93 +/- 0.036）。 [C-11] FMZ绑定在所有时间点都在控制范围内。仅在缺血性核中6小时后才观察到[F-18] FMISO保留率显着（1.16 +/- 0.091，p <0.05），随后变成梗塞。结论：ET1注射可产生可再现，缓慢发展的缺血性病变，并具有持续的低灌注水平。这项多示踪剂微型PET研究表明，ET1模型适用于诱发慢性外接缺血性病变，但似乎不适合研究急性中风的病理生理。 （C）2016 S.Karger AG，巴塞尔

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