Project: Altered Chloride homeostasis in Reactive plasticity upOn BrAin Trauma

Acronym	ACRoBAT
Duration	01/01/2017 - 30/09/2020
Project Topic	Progressive network reorganization and altered proliferation may stand for traumatic brain injury (TBI)-related complications, such as post-traumatic epilepsy and cognitive impairment. The proposed project aims at defining the contribution of altered chloride homeostasis and GABAergic transmission in TBI-triggered reactive plasticity mechanisms, from cellular to system levels. Our working hypothesis is that TBI induces changes in the chloride regulatory proteins KCC2 and NKCC1 leading to altered intracellular chloride homeostasis and changes in the polarity of GABAA mediated responses. This leads to hyper-excitability as well as requirement by neurons (principal and interneurons) for BDNF trophic support. This is set by GABAA depolarization dependent p75NTR pro-apoptotic signaling. Interneuron apoptosis also result in hyper-excitability and may increase proliferation in the DG. .A major focus of this project is to understand how these processes may contribute to rhythmopathies and epileptogenesis. We address these questions using a combination of state of the art transgenic tools for both temporal and cell specific control and monitoring of intracellular chloride as well as chloride regulatory proteins. This will be combined with advanced in vivo electrophysiological recordings and time-frequency analysis. Ultimately, we will test the therapeutic relevance of novel compounds acting on KCC2 functional expression.
Network	NEURON Cofund
Call	Call for Proposals for "European Research Projects on External Insults to the Nervous System"

Project partner

Number	Name	Role	Country
1	National Institute of Health and Medical Research	Coordinator	France
2	National Institute of Health and Medical Research	Partner	France
3	The Francis Crick Institute	Partner	United Kingdom
4	University Hospital Jena	Partner	Germany
5	The Spanish National Research Council	Partner	Spain