Rôle du dérèglement de l’homéostasie des ions chlorures sur l’inflammation induite dans un modèle de traumatisme crânien

Abstract: Bumetanide, an inhibitor of the Na-K-Cl cotransporter, has important positive effects on the physiopathology of many neurological disorders. The objective of my work was first to study the kinetics of the inflammatory response following traumatic brain injury (TBI). Then, to see if this treatment could influence this inflammatory process, with the aim of improving the memory disorders that patients experience in the chronic phase of a TBI.
For this purpose, controlled cortical impacted (CCI) animals were treated with bumetanide during the first post-traumatic week. I used immunohistochemical, flow cytometry, and ELISA techniques to study adult neurogenesis and the morphology and phenotype of astrocytes and microglia. I observed microglial cell motility with in vivo imaging. Finally, I performed telemetric EEG and behavioral tests to study the consequences on brain connectivity and the impact on cognitive performance. We showed that the imbalance of adult neurogenesis in the hippocampus induced by CCI, and the decrease in neuronal production are countered by bumetanide. The treatment also limits the massive loss of PV interneurons. We show that this could be related to the increase in the production of BDNF produced by microglia, and the increase in the number of contacts with PV interneurons. Finally, bumetanide prevents the onset of memory impairment and theta band changes in the chronic phase of the TBI.
We reveal here a new mechanism of action of bumetanide mediated by an acceleration of microglia activation after TBI. That leads to a neuroprotective action, contributing to the improvement of cognitive performance.

Jury:

Chairman – Prof. Valéry Matarazzo – Inmed, Marseille

Reporter – Dr Gilles Huberfeld, Cirb, Paris

Reporter – Dr Sabine Lévi, P3Cell, Paris

Reviewer – Prof. Agnès Nadjar, Neurocentre Magendie, Bordeaux

Thesis Co-Director – Christophe Pellegrino, Inmed, Marseille

Thesis Co-Director – Claudio Rivera, Inmed, Marseille

Marien Tessier, Early activity in the developing brain – Roustem Khazipov

Conference room – Inmed

Tuesday, December 7th at 2pm