Effect of nitric oxide modulators on cerebrospinal fluid outflow through the cribriform plate of C57Bl/6 mice

D. V. Petrovsky, V. A. Kim, M. B. Sharapova, D. S. Zuev, A. Z. Ibrayeva, E. K. Silvanovich, M. P. Moshkin, A. Romashchenko
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Abstract

Introduction. Beside the excretion of metabolic wastes, the lymphatic system in CNS play a crucial role in the regulation of intracranial pressure that is vital for the organism. One of the possible pathways of cerebrospinal fluid (CSF) drainage is its flow through the foramen of the cribriform plate (CP) into the nasal cavity. Despite the significant contribution of the nasal tract to the overall dynamics of the liquor, not much is known about the mechanisms of this process and how it is regulated. Due to its influence on the tone of blood vessels and peristalsis of lymphatic vessels, nitric oxide (NO) is a powerful modulator of liquor outflow, but its effects on nasal CSF outflow have not been studied yet. Aim and Methods. Using diffusion-weighted magnetic resonance imaging (DW MRI), we characterized the changes in CSF outflow through the CP of C57Bl/6 mice influenced by intranasal application of NO synthesis modulators. Results. In our study, using DW MRI and computer tomography (CT) mapping of the CP, we detected significant CSF outflow through its large dorsal and ventral foramen located along the nasal septum. At the same time, the CSF flow rate through the dorsal orifices of the CP was the highest. In addition, we showed that intranasal introduction of NO donor after 30 min leads to a significant decrease of water diffusion through the CP whereas application of a nonspecific NO synthase inhibitor into the nasal cavity enhances nasal outflow. The effects of the NO modulators did not have any significant spatial patterns; CSF outflow was significantly altered across all CP orifices regardless of their size or localization. Conclusion. The obtained results demonstrate the potential possibility of noninvasive local regulation of liquor dynamics, which may be used in the development of new approaches to the therapy of intracranial hypertension of various etiologies and methods of CNS detoxification.
一氧化氮调节剂对通过 C57Bl/6 小鼠楔形板流出脑脊液的影响
导言中枢神经系统的淋巴系统除了排泄代谢废物外,还在调节对机体至关重要的颅内压方面发挥着重要作用。脑脊液(CSF)引流的可能途径之一是通过楔形板(CP)孔流入鼻腔。尽管鼻腔对液体的整体动力学有重大贡献,但人们对这一过程的机制及其调节方式却知之甚少。由于一氧化氮(NO)对血管张力和淋巴管蠕动的影响,一氧化氮(NO)是液体外流的一个强有力的调节器,但其对鼻腔 CSF 外流的影响尚未得到研究。目的和方法。利用弥散加权磁共振成像(DW MRI),我们研究了鼻内注射一氧化氮合成调节剂对 C57Bl/6 小鼠脑脊液流出的影响。结果。在我们的研究中,我们使用 DW MRI 和计算机断层扫描(CT)绘制了 CP 的图谱,通过其位于鼻中隔沿线的背侧和腹侧大孔检测到大量 CSF 外流。同时,通过 CP 背侧孔的 CSF 流速最高。此外,我们还发现,30 分钟后鼻腔内引入 NO 供体会导致通过 CP 的水扩散显著减少,而向鼻腔内施用非特异性 NO 合酶抑制剂则会增强鼻腔外流。氮氧化物调节剂的影响没有明显的空间模式;无论 CP 孔的大小或位置如何,所有 CP 孔的 CSF 流出都发生了显著变化。结论研究结果表明,非侵入性局部液体动力学调节具有潜在的可能性,可用于开发治疗各种病因引起的颅内高压的新方法和中枢神经系统解毒方法。
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