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经髁后孔入路建立颅内注射用于脑肿瘤小鼠模型的新方法。

A novel method of intracranial injection via the postglenoid foramen for brain tumor mouse models.

机构信息

Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan.

出版信息

J Neurosurg. 2012 Mar;116(3):630-5. doi: 10.3171/2011.10.JNS11852. Epub 2011 Dec 9.

Abstract

OBJECT

Mouse models have been widely used in developing therapies for human brain tumors. However, surgical techniques such as bone drilling and skin suturing to create brain tumors in adult mice are still complicated. The aim of this study was to establish a simple and accurate method for intracranial injection of cells or other materials into mice.

METHODS

The authors performed micro CT scans and skull dissection to assess the anatomical characteristics of the mouse postglenoid foramen. They then used xenograft and genetically engineered mouse models to evaluate a novel technique of percutaneous intracranial injection via the postglenoid foramen. They injected green fluorescent protein-labeled U87MG cells or virus-producing cells into adult mouse brains via the postglenoid foramen and identified the location of the created tumors by using bioluminescence imaging and histological analysis.

RESULTS

The postglenoid foramen was found to be a well-conserved anatomical structure that allows percutaneous injection into the cerebrum, cerebellum, brainstem, and basal cistern in mice. The mean (± SD) time for the postglenoid foramen injection technique was 88 ± 15 seconds. The incidence of in-target tumor formation in the xenograft model ranged from 80% to 100%, depending on the target site. High-grade gliomas were successfully developed by postglenoid foramen injection in the adult genetically engineered mouse using virus-mediated platelet-derived growth factor B gene transfer. There were no procedure-related complications.

CONCLUSIONS

The postglenoid foramen can be used as a needle entry site into the brain of the adult mouse. Postglenoid foramen injection is a less invasive, safe, precise, and rapid method of implanting cells into the adult mouse brain. This method can be applied to both orthotopic xenograft and genetically engineered mouse models and may have further applications in mice for the development of therapies for human brain tumors.

摘要

目的

小鼠模型已广泛应用于开发人类脑肿瘤的治疗方法。然而,在成年小鼠中创建脑肿瘤的手术技术,如骨钻孔和皮肤缝合,仍然很复杂。本研究旨在建立一种简单而准确的方法,将细胞或其他物质经皮内注射到小鼠颅内。

方法

作者进行了微 CT 扫描和颅骨解剖,以评估小鼠髁后孔的解剖特征。然后,他们使用异种移植和基因工程小鼠模型,通过髁后孔评估一种新的经皮颅内注射技术。他们通过髁后孔将绿色荧光蛋白标记的 U87MG 细胞或产生病毒的细胞注射到成年小鼠脑内,并通过生物发光成像和组织学分析来确定所创建肿瘤的位置。

结果

髁后孔是一种保守的解剖结构,允许经皮注射到小鼠的大脑、小脑、脑干和基底池。髁后孔注射技术的平均(± SD)时间为 88 ± 15 秒。在异种移植模型中,根据目标部位的不同,肿瘤形成的靶向率为 80%至 100%。通过髁后孔注射病毒介导的血小板衍生生长因子 B 基因转移,在成年基因工程小鼠中成功地建立了高级别胶质瘤。没有与手术相关的并发症。

结论

髁后孔可作为成年小鼠大脑内的进针部位。髁后孔注射是一种侵袭性较小、安全、精确和快速的将细胞植入成年小鼠大脑的方法。该方法可应用于原位异种移植和基因工程小鼠模型,并且可能在用于开发人类脑肿瘤治疗方法的小鼠中具有进一步的应用。

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