慢性脑室内给药是一种可靠的猴子脑研究方法

Lin-Heng Zhang, Hong‐Yi Yang, Jing Wu, Yun Wu, Luwan Wang, Haiyang Tong, Jin Zhang, Wenchao Wang, Rongyao Huang, Jiang-Lei Xu, Jing Su, Xun-Ran Luo, Yong Yin, Shi-Hao Wu, Xinyong Hu
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摘要

脑室内(ICV)给药是将被血脑屏障阻断的大分子和物质直接输送到中枢神经系统(CNS)的一种方法。它被广泛用于猴子的大脑研究。然而,这种方法是侵入性的,因为它需要在大脑中植入引导管。长期植入导管和给予分子递送载体(通常是生理盐水)是否会通过诱导慢性中枢神经系统炎症甚至更严重的脑萎缩来影响大脑,这仍然是一个有待解决的问题。为了回答这个问题,在另一项研究中,我们研究了3只接受插管植入和1年ICV生理盐水治疗的对照组猴子的炎症标志物和大脑结构。实验期间,定期采集猕猴脑脊液(CSF)标本,采用电化学发光免疫法检测3种经典炎症标志物(IL-1β、IL-6、TNF-α)水平。采用9.4特斯拉(Tesla)磁共振成像定期对活体猴子进行脑结构成像,该成像可提供活体猴子最高分辨率的磁共振图像,并测量海马体积以评估脑萎缩情况。数据显示,在给药期间,脑脊液中炎症标志物的长期水平和海马体积与基线相比没有显著变化。这些结果表明,长期通过插管给药生理盐水不会引起恒河猴的慢性神经炎症或脑萎缩,提示通过植入插管给药慢性ICV是一种可靠的猴子脑研究方法。
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Chronic intracerebroventricular administration is a reliable method in brain studies on monkeys
Intracerebroventricular (ICV) administration through cannulas is a direct way to deliver large molecules and substances that are blocked by the blood-brain barrier into the central nervous system (CNS). It is widely used in brain studies on monkeys. However, this method is invasive, as it requires guide cannulas to be implanted into the brain. Whether the long-term implantation of the cannula and the administration of molecule-delivering vehicles, usually saline, can affect the brain by inducing chronic CNS inflammation or even worse brain atrophy, remains an issue to be solved. To answer this question, we investigated inflammatory markers and brain structures on three vehicle-control monkeys who received cannula implantation and one-year ICV saline administration in another study. During the experiment, the monkeys’ cerebrospinal fluid (CSF) samples were collected periodically, and the level of three classic inflammatory markers (IL-1β, IL-6, and TNF-α) were measured by electrochemiluminescence immunoassay. The monkeys’ brain structures were imaged in vivo periodically by 9.4 Tesla magnetic resonance imaging, which can provide the best-resolution magnetic resonance images of living monkeys, and the volume of the hippocampus was measured to evaluate the brain atrophy. The data reveal that, during the administrating period, the long-term levels of the inflammatory markers in the CSF and the volumes of the hippocampus did not change significantly compared with the baseline. These results suggest that the long-term ICV administration of saline through cannulas did not induce chronic neuroinflammation or brain atrophy in these rhesus monkeys, suggesting chronic ICV administration via implanted cannulas is a reliable method in monkey brain research.
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