Objective
Hepatic Encephalopathy (HE) A is a neuropsychiatric syndrome occurring in both acute and chronic liver failure that includes behavioural, mental and motor disturbances. The more typical motor abnormalities observed are flapping tremor or cortico- spinal signs (exaggerated deep tendon reflexes, Babinski's signs). Those abnormalities significantly diminish the quality of life of the patients.
Clinical studies led by the host of this fellowship have suggested that a low grade brain oedema along the glutamatergic cortiCOspinal tract (CST) is responsible for the abnormal cortico-spinal functions observed in patients with chronic liver disease. Thus we propose to study the physiological, morphological and neurochemical changes that occur in the CST of an experimental model of chronic liver failure and try to correlate them with brain oedema. We will use immunohistochemical, electrophysiological and microdialysis techniques to assess the effect of chronic liver failure on:
(1) the integrity of the cortico-spinal neurons
(2) the degree of myelination of the CST;
(3) the levels of expression of the glial and neuronal glutamate transporters and ionotropic receptors at different levels of the CST;
(4) the release of glutamate upon electrostimulation in the motor cortex and in the spinal cord (5) the cortico-spinal function.
Finally we will try link the electrophysiologic abnormalities to the brain oedema of the CST by using an oedema-lowering therapy.
This project will help of a young French researcher who did his PhD in Canada, to come back to Europe and to complete his training. It will also allow the transfer to the host of the technical knowledge he acquired there. Also the risk of chronic liver diseases is increasing in Europe and is already high in upcoming new members of the European Union. Therefore, increasing our basic knowledge of HE now, will be important for the near future to help design new therapeutic strategies.
Fields of science (EuroSciVoc)
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Keywords
Call for proposal
FP6-2002-MOBILITY-5
See other projects for this call
Funding Scheme
EIF - Marie Curie actions-Intra-European FellowshipsCoordinator
BARCELONA
Spain