Continuous positive airway pressure increases CSF flow and glymphatic transport
Burhan Ozturk, Sunil Koundal, Ehab Al Bizri, Xinan Chen, Zachary Gursky, Feng Dai, Andrew Lim, Paul Heerdt, Jonathan Kipnis, Allen Tannenbaum, Hedok Lee, Helene Benveniste
Burhan Ozturk, Sunil Koundal, Ehab Al Bizri, Xinan Chen, Zachary Gursky, Feng Dai, Andrew Lim, Paul Heerdt, Jonathan Kipnis, Allen Tannenbaum, Hedok Lee, Helene Benveniste
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Research Article Neuroscience

Continuous positive airway pressure increases CSF flow and glymphatic transport

Abstract

Respiration can positively influence cerebrospinal fluid (CSF) flow in the brain, yet its effects on central nervous system (CNS) fluid homeostasis, including waste clearance function via glymphatic and meningeal lymphatic systems, remain unclear. Here, we investigated the effect of supporting respiratory function via continuous positive airway pressure (CPAP) on glymphatic-lymphatic function in spontaneously breathing anesthetized rodents. To do this, we used a systems approach combining engineering, MRI, computational fluid dynamics analysis, and physiological testing. We first designed a nasal CPAP device for use in the rat and demonstrated that it functioned similarly to clinical devices, as evidenced by its ability to open the upper airway, augment end-expiratory lung volume, and improve arterial oxygenation. We further showed that CPAP increased CSF flow speed at the skull base and augmented glymphatic transport regionally. The CPAP-induced augmented CSF flow speed was associated with an increase in intracranial pressure (ICP), including the ICP waveform pulse amplitude. We suggest that the augmented pulse amplitude with CPAP underlies the increase in CSF bulk flow and glymphatic transport. Our results provide insights into the functional crosstalk at the pulmonary-CSF interface and suggest that CPAP might have therapeutic benefit for sustaining glymphatic-lymphatic function.

Authors

Burhan Ozturk, Sunil Koundal, Ehab Al Bizri, Xinan Chen, Zachary Gursky, Feng Dai, Andrew Lim, Paul Heerdt, Jonathan Kipnis, Allen Tannenbaum, Hedok Lee, Helene Benveniste

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Figure 3

CPAP induces an increase in ICP and pulse pressure amplitude.

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CPAP induces an increase in ICP and pulse pressure amplitude. (A) Schema...
(A) Schematic illustration of setup. (B) Representative ICP waveform recorded from the pressure probe at baseline showing the pulse and respiratory oscillations on the ICP waveform (red) with parallel recording of respiration (blue) and HR via pulse oximetry (green). The gray dashed line indicates the baseline ICP opening pressure approximately 1 mmHg recorded from a separate rat not undergoing CPAP. (C) Corresponding ICP waveforms from the rat shown in B, while breathing with a CPAP pressure of 3 cmH2O. The average ICP pressure and pulse amplitude are noticeably increased with the applied CPAP pressure. (D) Increase in the mean ICP pressure from baseline with application of CPAP from n = 4 rats (1 rat was excluded due to baseline drifting during the experiment). (E) Comparison of changes from baseline in the mean respiratory amplitude and mean pulse amplitude (normalized to baseline) with CPAP. An independent t test revealed that there were no differences in the respiratory amplitude with CPAP; however, the arterial pulse amplitude increased significantly from baseline with CPAP (*P = 0.0315).