A novel chronic dural port platform for continuous collection of cerebrospinal fluid and intrathecal drug delivery in free-moving mice.
A novel chronic dural port platform for continuous collection of cerebrospinal fluid and intrathecal drug delivery in free-moving mice.
复制标题
一种新型的慢性硬膜端口平台，可连续收集自由移动小鼠的脑脊液和鞘内药物的递送。
DOI：
10.1186/s12987-022-00331-1
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发表时间：
2022-05-03
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
脑脊液（CSF）提供了发生在中枢神经系统（CNS）的病理生理变化的密切代表;因此，它已被用于CNS疾病的发病机制研究和生物标志物开发。从与CNS疾病相关的有效小鼠模型获得的CSF可以是成功的生物标志物和药物开发的重要资源。然而，可以从微小的鞘内空间收集的有限体积的CSF和CSF取样中涉及的技术困难一直是阻碍小鼠模型中CSF的详细分析的瓶颈。我们开发了一种新的慢性硬脑膜端口（CDP）的方法，没有插管的CSF收集小鼠。这种方法可以轻松、重复地进入自由活动、未麻醉的小鼠的鞘内空间，从而能够在组织损伤最小的情况下连续长期收集CSF，并从一只小鼠中提供大量高质量的CSF。当与化学生物传感器相结合时，CDP方法允许在自由移动的小鼠中以一秒的时间分辨率实时监测CSF中神经化学物质的动态变化。此外，CDP可以作为鞘内注射CSF示踪剂和药物的直接接入点。我们建立了CDP植入和连续CSF收集方案。使用CDP采集的CSF未被血液污染，并保持了生理浓度的基础电解质和蛋白质。CDP方法不影响小鼠的生理行为或诱导组织损伤，从而能够稳定收集CSF长达四周。使用CDP递送的CSF示踪剂的时空分布揭示了CSF在不同脑区中的代谢是动态的。使用CDP直接鞘内递送中枢作用药物使得能够在自由活动的小鼠中进行实时行为评估。CDP方法能够收集大量高质量CSF，并在自由活动小鼠中直接鞘内给药，同时进行实时行为评估。结合中枢神经系统疾病相关的动物模型，该方法为生物标志物和治疗药物的研究提供了一个独特而有价值的平台。在线版本包含补充材料，可通过10.1186/s12987-022-00331-1获得。
Cerebrospinal fluid (CSF) provides a close representation of pathophysiological changes occurring in the central nervous system (CNS); therefore, it has been employed in pathogenesis research and biomarker development for CNS disorders. CSF obtained from valid mouse models relevant to CNS disorders can be an important resource for successful biomarker and drug development. However, the limited volume of CSF that can be collected from tiny intrathecal spaces and the technical difficulties involved in CSF sampling has been a bottleneck that has hindered the detailed analysis of CSF in mouse models. We developed a novel chronic dural port (CDP) method without cannulation for CSF collection of mice. This method enables easy and repeated access to the intrathecal space in a free-moving, unanesthetized mouse, thereby enabling continuous long-term CSF collection with minimal tissue damage and providing a large volume of high-quality CSF from a single mouse. When combined with chemical biosensors, the CDP method allows for real-time monitoring of the dynamic changes in neurochemicals in the CSF at a one-second temporal resolution in free-moving mice. Moreover, the CDP can serve as a direct access point for the intrathecal injection of CSF tracers and drugs. We established a CDP implantation and continuous CSF collection protocol. The CSF collected using CDP was not contaminated with blood and maintained physiological concentrations of basic electrolytes and proteins. The CDP method did not affect mouse’s physiological behavior or induce tissue damage, thereby enabling a stable CSF collection for up to four weeks. The spatio-temporal distribution of CSF tracers delivered using CDP revealed that CSF metabolism in different brain areas is dynamic. The direct intrathecal delivery of centrally acting drugs using CDP enabled real-time behavioral assessments in free-moving mice. The CDP method enables the collection of a large volume of high-quality CSF and direct intrathecal drug administration with real-time behavioral assessment in free-moving mice. Combined with animal models relevant to CNS disorders, this method provides a unique and valuable platform for biomarker and therapeutic drug research. The online version contains supplementary material available at 10.1186/s12987-022-00331-1.
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影响因子：
4.6
作者：
Fu K;Miyamoto Y;Otake K;Sumi K;Saika E;Matsumura S;Sato N;Ueno Y;Seo S;Uno K;Muramatsu SI;Nitta A
通讯作者：
Nitta A
影响因子：
11.2
作者：
Takeda, Shuko;Commins, Caitlin;Hyman, Bradley T.
通讯作者：
Hyman, Bradley T.
DOI：
10.1016/j.bbadis.2015.10.014
发表时间：
2016-03
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Simon MJ;Iliff JJ
通讯作者：
Iliff JJ
影响因子：
5
作者：
Kiyatkin, Eugene A.;Wakabayashi, Ken T.
通讯作者：
Wakabayashi, Ken T.
影响因子：
--
作者：
Myers, Ariana;McGonigle, Paul
通讯作者：
McGonigle, Paul