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一种改良的经颅大脑中动脉闭塞模型,用于研究老年小鼠的卒中结局。

A Modified Transcranial Middle Cerebral Artery Occlusion Model to Study Stroke Outcomes in Aged Mice.

机构信息

Multidisciplinary Brain Protection Program, Department of Anesthesiology, Duke University Medical Center;

Multidisciplinary Brain Protection Program, Department of Anesthesiology, Duke University Medical Center.

出版信息

J Vis Exp. 2023 May 5(195). doi: 10.3791/65345.

DOI:10.3791/65345
PMID:37212591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10913267/
Abstract

In experimental stroke research, middle cerebral artery occlusion (MCAO) with an intraluminal filament is widely used to model ischemic stroke in mice. The filament MCAO model typically exhibits a massive cerebral infarction in C57Bl/6 mice that sometimes includes brain tissue in the territory supplied by the posterior cerebral artery, which is largely due to a high incidence of posterior communicating artery atresia. This phenomenon is considered a major contributor to the high mortality rate observed in C57Bl/6 mice during long-term stroke recovery after filament MCAO. Thus, many chronic stroke studies exploit distal MCAO models. However, these models usually produce infarction only in the cortex area, and consequently, the assessment of post-stroke neurologic deficits could be a challenge. This study has established a modified transcranial MCAO model in which the MCA at the trunk is partially occluded either permanently or transiently via a small cranial window. Since the occlusion location is relatively proximal to the origin of the MCA, this model generates brain damage in both the cortex and striatum. Extensive characterization of this model has demonstrated an excellent long-term survival rate, even in aged mice, as well as readily detectable neurologic deficits. Therefore, the MCAO mouse model described here represents a valuable tool for experimental stroke research.

摘要

在实验性中风研究中,使用管内线栓法的大脑中动脉闭塞(MCAO)广泛用于在小鼠中模拟缺血性中风。线栓 MCAO 模型通常在 C57Bl/6 小鼠中引起大面积脑梗死,有时包括后交通动脉闭塞导致的后循环供血区脑组织梗死,这主要是由于后交通动脉发生率高所致。这种现象被认为是导致线栓 MCAO 后长期中风恢复过程中 C57Bl/6 小鼠死亡率高的主要原因。因此,许多慢性中风研究利用远端 MCAO 模型。然而,这些模型通常仅在皮质区域产生梗死,因此,中风后神经功能缺损的评估可能是一个挑战。本研究建立了一种改良的经颅 MCAO 模型,通过一个小的颅窗永久性或短暂性地部分闭塞 MCA 干。由于闭塞位置相对靠近 MCA 的起源处,因此该模型可在皮质和纹状体中引起脑损伤。该模型的广泛特征表明,即使在老年小鼠中,也具有出色的长期存活率和易于检测的神经功能缺损。因此,这里描述的 MCAO 小鼠模型代表了实验性中风研究的一种有价值的工具。

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Beneficial effects of neuronal ATF6 activation in permanent ischemic stroke.神经元ATF6激活在永久性缺血性卒中中的有益作用。
Front Cell Neurosci. 2022 Oct 14;16:1016391. doi: 10.3389/fncel.2022.1016391. eCollection 2022.
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Single-cell transcriptomic analysis of the immune cell landscape in the aged mouse brain after ischemic stroke.单细胞转录组分析缺血性脑卒中后老年鼠脑免疫细胞图谱
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Post-ischemia common carotid artery occlusion worsens memory loss, but not sensorimotor deficits, in long-term survived stroke mice.缺血后颈总动脉闭塞加重长期存活中风小鼠的记忆丧失,但不加重感觉运动缺陷。
Brain Res Bull. 2022 Jun 1;183:153-161. doi: 10.1016/j.brainresbull.2022.03.008. Epub 2022 Mar 16.
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Circulation. 2022 Feb 22;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. Epub 2022 Jan 26.
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Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.缺血性脑卒中后,增加 O-GlcNAcylation 对年轻和老年大脑具有神经保护作用。
Exp Neurol. 2021 May;339:113646. doi: 10.1016/j.expneurol.2021.113646. Epub 2021 Feb 15.
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