The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion

Chiang, Huihua Kenny; Wu, Kuo-Chen; Chen, You‐Yin; Ho, Chin-Jui; Wang, Hanlin; Fu, Yuhua; Chen, Wenyu; Lin, Chien-Ching

doi:10.1007/s11095-023-03565-2

Pharm Res

2023

DOI: 10.1007/s11095-023-03565-2

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The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion

Huihua Kenny Chiang¹,

Kuo-Chen Wu²,

You‐Yin Chen³

et al.

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2024

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40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice

Sun,

Dias,

Peng

et al. 2024

Cell Discov

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The glymphatic-lymphatic system is increasingly recognized as fundamental for the homeostasis of the brain milieu since it defines cerebral spinal fluid flow in the brain parenchyma and eliminates metabolic waste. Animal and human studies have uncovered several important physiological factors regulating the glymphatic system including sleep, aquaporin-4, and hemodynamic factors. Yet, our understanding of the modulation of the glymphatic system is limited, which has hindered the development of glymphatic-based treatment for aging and neurodegenerative disorders. Here, we present the evidence from fluorescence tracing, two-photon recording, and dynamic contrast-enhanced magnetic resonance imaging analyses that 40 Hz light flickering enhanced glymphatic influx and efflux independently of anesthesia and sleep, an effect attributed to increased astrocytic aquaporin-4 polarization and enhanced vasomotion. Adenosine-A2A receptor (A2AR) signaling emerged as the neurochemical underpinning of 40 Hz flickering-induced enhancement of glymphatic flow, based on increased cerebrofluid adenosine levels, the abolishment of enhanced glymphatic flow by pharmacological or genetic inactivation of equilibrative nucleotide transporters-2 or of A2AR, and by the physical and functional A2AR–aquaporin-4 interaction in astrocytes. These findings establish 40 Hz light flickering as a novel non-invasive strategy of enhanced glymphatic flow, with translational potential to relieve brain disorders.

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40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice

Sun,

Dias,

Peng

et al. 2024

Cell Discov

View full text Add to dashboard Cite

show abstract

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The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion

Cited by 1 publication

References 55 publications

40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice

40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice

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