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首页> 外文期刊>Journal of stroke and cerebrovascular diseases: The official journal of National Stroke Association >Acute Studies of a New Primate Model of Reversible Middle Cerebral Artery Occlusion
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Acute Studies of a New Primate Model of Reversible Middle Cerebral Artery Occlusion

机译:新型可逆中脑动脉闭塞灵长类动物模型的急性研究

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The recent failure of many clinical trials of neuroprotective compounds may be due in part to poor animal models of human stroke, We have developed an endovas-cular stroke model in nonhuman primates that is compatible with serial magnetic resonance imaging (MRI) monitoring. Using cynomologous macaques (n = 4), a microcatheter was navigated transarterially (under fluoroscopic guidance) from the femoral artery to the middle cerebral artery (MCA). The microcatheter was wedged in a branch of the MCA for 3 hours to cause focal cerebral ischemia, as verified angiographically. During occlusion and/or reperfusion, animals were scanned with MRI, and imaging findings were compared with the stained brain sections. All animals demonstrated small stroke lesions in the expected vascular territory, as seen on diffusion-weighted MRI and confirmed by postmortem examination, Reperfusion after 3 hours was confirmed angiographically (n - 2) and also by MRI (n = 4). The mean initial lesion volume, measured on the postreperfusion MRI scans, was 2,3 ± 1.3 mL (n = 4). There was good agreement between anatomic location of the lesion on MRI and postmortem histological staining (n = 3). A "minimally invasive" primate model of focal cerebral ischemia was developed that is ideally suited to MRI studies of both acute and chronic stroke. By using serial MRI scans to measure changes in lesion size over time, we will be able to control for variability in lesion size/location. This model should prove useful as a test bed for new stroke therapies, in which noninvasive imaging findings are readily comparable to human stroke.
机译:神经保护性化合物的许多临床试验最近的失败可能部分归因于人类中风的不良动物模型。我们开发了与串行磁共振成像(MRI)监测兼容的非人类灵长类动物的血管内中风模型。使用猕猴(n = 4),从股动脉到大脑中动脉(MCA)穿刺(在荧光镜引导下)微导管。将微导管楔入MCA的分支中3个小时,以引起局灶性脑缺血,如血管造影证实。在闭塞和/或再灌注期间,对动物进行MRI扫描,并将影像学发现与染色的脑切片进行比较。在弥散加权MRI上观察并通过事后检查证实,所有动物均在预期的血管区域显示出中风小损伤,通过血管造影(n-2)以及MRI(n = 4)证实了3小时后的再灌注。在再灌注后MRI扫描中测得的平均初始病变体积为2.3±1.3 mL(n = 4)。 MRI上病变的解剖位置与死后组织学染色之间有很好的一致性(n = 3)。已开发出局灶性脑缺血的“微创”灵长类动物模型,非常适合急性和慢性卒中的MRI研究。通过使用连续MRI扫描测量病变随时间的变化,我们将能够控制病变大小/位置的变化。这种模型应被证明可作为新的中风疗法的试验床,其中非侵入性影像学发现很容易与人类中风媲美。

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