Author:
Hadjihambi Anna,Harrison Ian F.,Arias Natalia,Gallego-Durán Rocío,Hosford Patrick S.,Davies Nathan,Habtesion Abeba,Lythgoe Mark F.,Gourine Alexander V.,Jalan Rajiv
Abstract
AbstractNeuronal function is exquisitely sensitive to alterations in extracellular environment. In patients with hepatic encephalopathy (HE), accumulation of metabolic waste products and noxious substances in the interstitial fluid of the brain may contribute to neuronal dysfunction and cognitive impairment. In a rat model of chronic liver disease, we used an emerging dynamic contrast-enhanced MRI technique to assess the efficacy of the glymphatic system, which facilitates clearance of solutes from the brain. We identified discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of altered glymphatic flow, which aligned with cognitive/behavioural deficits. Although the underlying pathophysiological mechanisms remain unclear, this study provides the first experimental evidence of impaired glymphatic clearance in HE.
Publisher
Cold Spring Harbor Laboratory