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Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion / 神经科学通报·英文版
Neuroscience Bulletin ; (6): 181-199, 2022.
Article Dans Anglais | WPRIM | ID: wpr-922672
ABSTRACT
The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Encéphalopathie ischémique / Sténose carotidienne / Digoxine / Modèles animaux de maladie humaine / Dysfonctionnement cognitif / Substance blanche / Souris de lignée C57BL Limites du sujet: Animaux langue: Anglais Texte intégral: Neuroscience Bulletin Année: 2022 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Encéphalopathie ischémique / Sténose carotidienne / Digoxine / Modèles animaux de maladie humaine / Dysfonctionnement cognitif / Substance blanche / Souris de lignée C57BL Limites du sujet: Animaux langue: Anglais Texte intégral: Neuroscience Bulletin Année: 2022 Type: Article