Liver Disease is the one chronic disorder that's increasing in frequency with a steady rise in deaths each year.

Professor Roger Williams CBE

The Liver-Brain Axis

Team Leader | Dr Anna Hadjihambi

Team:
  • Christos Konstantinou 
  • Matthew Siddle
  • Deepika Goel 

The main project of the group uses state-of-the-art in vivo, molecular and imaging techniques, combined with human data analysis in order to investigate the pathological mechanisms underlying the effects of NAFLD on the cerebrovascular and brain function. The aim is to obtain knowledge that will lead to the development of novel and effective neuroprotective therapies. 

Projects:

  1. “Is fatty liver disease increasing our risk of developing neurodegenerative conditions?” This project addresses the hypothesis that gut microbiome perturbations in NAFLD/NASH will induce systemic and brain inflammation lowering the threshold for developing diseases like Parkinson’s and Alzheimer’s disease.
  2. Understanding the mechanisms underlying NAFLD-associated brain dysfunction and the potential of its reversibility following liver disease resolution during ageing.

Collaborations:

  1. Dr Vishal Patel: Development of novel non-invasive methods for the diagnosis of hepatic encephalopathy
  2. Dr Antonio Riva: Bacterial translocation and brain dysfunctions in liver disease

Publications:

Hadjihambi A., Konstantinou C., Klohs J., Monsorno K., Guennec L. A., Donnelly C., et. al. 2022. Partial MCT1 invalidation protects against diet-induced non-alcoholic fatty liver disease and the associated brain dysfunction. J Hepatol; 78 (1): 180-190. https://doi.org/10.1016/j.jhep.2022.08.008.

Hadjihambi A. 2021. Cerebrovascular alterations in NAFLD: Is it increasing our risk of Alzheimer’s disease?. Anal Biochem, 636: 114387. https://doi.org/10.1016/j.ab.2021.114387

Hadjihambi A., Pierzchala K., Cudalbu C., Simicic D., Donnelly C., Konstantinou C., et. al. 2022. Ammonia impairs brain oxygenation in an animal model of minimal hepatic encephalopathy. J Hepatol Reports; 4 (8): 100509. https://doi.org/10.1016/j.jhepr.2022.100509

Hadjihambi, A., Karagiannis, A., Theparambil, S. M., Ackland, G. L. & Gourine, A. V. The effect of general anaesthetics on brain lactate release. Eur J Pharmacol; 881:173188. https://doi.org/10.1016/j.ejphar.2020.173188

Hadjihambi A., Harrison I. F., Costas-Rodriguez M., Vanhaecke F., Arias N., Gallego[1]Duran R., et al. 2018. Impaired brain glymphatic flow in experimental hepatic encephalopathy. J Hepatol;70(1):40-49. https://doi.org/10.1016/j.jhep.2018.08.021

Hadjihambi, A., De Chiara, F., Hosford, P. S., Habtetion, A., Karagianis, A., Davies, H., et al. 2017. Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease. Hepatology, 65, 1306-1318. https://doi.org/10.1002/hep.2903126/1/2023

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