We aim to identify the mechanisms by which liver diseases lead to cognitive and motor impairment in patients with minimal hepatic encephalopathy (MHE) and new treatments for MHE.
We showed that:
- A) MHE appearance in patients is due to a pro-inflammatory shift in peripheral inflammation;
- B) hyperammonemia induces inflammation and neuroinflammation, which lead to cognitive and motor impairment.
- C) peripheral inflammation induces neuroinflammation, increasing inflammatory factors in cerebellum and hippocampus that alter glutamate and GABA neurotransmission, membrane expression of glutamate and GABA receptors and transporters and extracellular levels. This leads to cognitive and motor impairment. We reversed neurological impairment by reducing inflammation with anti-TNFα or anti-IL-17 and acting on 10 brain targets identified in our studies.
- D) plasma extracellular vesicles (EV) from hyperammonemic rats, injected to control rats, induce neuroinflammation and cognitive and motor impairment, supporting that EV play a key role in the transmission of peripheral alterations to brain and in neurological impairment.
We are extending our studies to Parkinson’s disease. Some questions that we are studying are:
- Which peripheral alterations are responsible for MHE induction?
- How these peripheral alterations are transmitted to the brain?
- How this induces neuroinflammation?
- How neuroinflammation impairs neurotransmission?
- How impaired neurotransmission leads to cognitive and motor impairment?
PRESENTATION
GET TO KNOW US BETTER
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Dr. Vicente Felipo Lab Presentation
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Patent for a method for early diagnosis of EHM
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RESEARCH STAFF
THE PEOPLE WHO MAKE IT ALL POSSIBLE
Vicente Felipo Orts
vfelipo@cipf.es
Marta Llansola Gil
mllansola@cipf.es
Amparo Urios Lluch
aurios@cipf.es
Yaiza Arenas Ortiz
ymarenas@cipf.es
Maria Mar Martínez García
mmartinezg@cipf.es
Gergana Mincheva Ganeva
givaylova@cipf.es
María ángeles Pedrosa Sánchez
mapedrosa@cipf.es
Andrea Palomares Rodríguez
apalomares@cipf.es
Daniela A. Batallas Ureña
dbatallas@cipf.es
Reza Azadnasab
razadnasab@cipf.es
PUBLICATIONS
OUR SCIENTIFIC CONTRIBUTIONS
A transient blood IL-17 increase triggers neuroinflammation in cerebellum and motor incoordination in hyperammonemic rats.
Journal of Neuroinflammation 2024 Nov, DOI: 10.1186/s12974-024-03310-5, Vol. 21, pag. 314-314
Extracellular vesicles from hyperammonemic rats induce neuroinflammation in hippocampus and impair cognition in control rats.
CELLULAR AND MOLECULAR LIFE SCIENCES 2023 Mar, DOI: 10.1007/s00018-023-04750-7, Vol. 80, pag. 90-90
Hepatic encephalopathy
Nature Reviews Disease Primers 2022 Jun, DOI: 10.1038/s41572-022-00366-6, Vol. 8, pag. 43-43
