Could dexmedetomidine be repurposed as a glymphatic enhancer?

Persson, Niklas Daniel Åke; Uusalo, Panu; Nedergaard, Maiken; Lohela, Terhi J.; Lilius, Tuomas

doi:10.1016/j.tips.2022.09.007

Cited by 22 publications

(18 citation statements)

References 79 publications

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“…The effects of general anesthesia on the glymphatic system are complex and multifaceted, as different anesthetic agents have been shown to alternately enhance and suppress glymphatic activity. Several studies have found that the anesthetic dexmedetomidine mimics the effects of slow-wave sleep and thus drives glymphatic activity ( Lilius et al, 2019 ; Persson et al, 2022 ). Other studies show that general anesthesia impairs glymphatic function by disrupting cerebral arterial pulsatility and respiration, processes that drive CSF-ISF exchange.…”

Section: Postoperative Cognitive Dysfunctionmentioning

confidence: 99%

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep

Campbell,

Figueiro

2024

Front. Neurosci.

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Postoperative cognitive dysfunction (POCD) is a neurological disorder characterized by the emergence of cognitive impairment after surgery. A growing body of literature suggests that the onset of POCD is closely tied to circadian rhythm disruption (CRD). Circadian rhythms are patterns of behavioral and physiological change that repeat themselves at approximately, but not exactly, every 24 h. They are entrained to the 24 h day by the daily light–dark cycle. Postoperative CRD affects cognitive function likely by disrupting sleep architecture, which in turn provokes a host of pathological processes including neuroinflammation, blood–brain barrier disturbances, and glymphatic pathway dysfunction. Therefore, to address the pathogenesis of POCD it is first necessary to correct the dysregulated circadian rhythms that often occur in surgical patients. This narrative review summarizes the evidence for CRD as a key contributor to POCD and concludes with a brief discussion of how circadian-effective hospital lighting can be employed to re-entrain stable and robust circadian rhythms in surgical patients.

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Section: Postoperative Cognitive Dysfunctionmentioning

confidence: 99%

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep

Campbell,

Figueiro

2024

Front. Neurosci.

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“…Ex vivo studies demonstrated varying effects of different anesthetics on the glymphatic influx . Isoflurane significantly inhibits the glymphatic influx, while dexmedetomidine promotes it. , However, the underlying mechanism remains unknown. The high time-spatial resolution of the in vivo NIR-II imaging model prompted us to reassess the impact of these two drugs on the glymphatic influx.…”

Section: Resultsmentioning

confidence: 99%

“…CSF flow rate varies at different inlet and outlet boundary conditions . The OB region serves as a primary boundary for the outflow of CSF. , We utilized the temporal slopes of MSI in the OB region as an indicator of CSF flow rate. The linear regression analysis revealed a positive correlation between the glymphatic influx (the MSIs of the brain region at 30 min) and CSF flow rate (the temporal slopes of MSI in the OB region) (Figure i), suggesting that decreased CSF flow rates augment the glymphatic influx.…”

Section: Resultsmentioning

confidence: 99%

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

Li,

Sun,

Zhang

et al. 2024

ACS Nano

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Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

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“…To determine whether this imaging technology has the potential to achieve real-time and dynamic assessment of the glymphatic system function, we monitored the well-established effect of anesthetic drugs on the glymphatic influx. ISO anesthesia inhibits the CSF influx in the brain, while Dex is used as a supplementary drug and is transported by intraperitoneal injection at a certain dose to enhance the glymphatic influx in the brain [ 16 , 17 , 37 – 39 ]. We primarily used NIR-II imaging to evaluate the enhancing role of Dex at a twice-daily administration dose of 0.015 mg/kg based on a previous report and we also tested the effect of different doses of Dex on the glymphatic system [ 17 ].…”

Section: Resultsmentioning

confidence: 99%

NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury

Sun,

Fang,

et al. 2024

J Nanobiotechnol

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The glymphatic system plays an important role in the transportation of cerebrospinal fluid (CSF) and the clearance of metabolite waste in brain. However, current imaging modalities for studying the glymphatic system are limited. Herein, we apply NIR-II nanoprobes with non-invasive and high-contrast advantages to comprehensively explore the function of glymphatic system in mice under anesthesia and cerebral ischemia–reperfusion injury conditions. Our results show that the supplement drug dexmedetomidine (Dex) enhances CSF influx in the brain, decreases its outflow to mandibular lymph nodes, and leads to significant differences in CSF accumulation pattern in the spine compared to isoflurane (ISO) alone, while both ISO and Dex do not affect the clearance of tracer-filled CSF into blood circulation. Notably, we confirm the compromised glymphatic function after cerebral ischemia–reperfusion injury, leading to impaired glymphatic influx and reduced glymphatic efflux. This technique has great potential to elucidate the underlying mechanisms between the glymphatic system and central nervous system diseases. Graphical Abstract

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Could dexmedetomidine be repurposed as a glymphatic enhancer?

Cited by 22 publications

References 79 publications

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx

NIR-II nanoprobes for investigating the glymphatic system function under anesthesia and stroke injury

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