PROJECT: JTC2014: BrIE

Brain Inflammation, Glia and Epilepsy

Abstract

The goal of this project is to understand how brain inflammation contributes to pathogenic events that result in focal epilepsy. Increasing evidence suggests that neuron-glia interactions are critical actors and targets of neuroinflammation that determine the pathophysiology of various neurological disorders, including epilepsy. We will combine molecular, genetic, imaging, neurophysiology and histochemical techniques to investigate astrocyte and microglia dysfunction in brain tissue obtained from post-surgical patient specimens with mesial temporal lobe epilepsy (MTLE) and in related animal models. We will: - study how inflammation impairs astrocyte K+ buffering during epileptogenesis - investigate how inflammation modulates glia Ca2+ signaling and transmitter release in MTLE - test the role of inflammasome and of microglia in blood-brain barrier disruption in models of MTLE - identify biomarkers of inflammation in MTLE The complementary approaches, which are not available at single laboratory level, will require exchanges of personnel, methods and materials between partners to achieve the research goals and to foster a European network of basic neuroscientists and neurologists focused on neuroinflammation and epilepsy. Investigating the impact of glia and inflammation in the pathogenesis and progression of focal epilepsies will lead to the identification of new biomarkers and targets for the development of alternative and more specific anti-epileptogenic therapies.

Keywords

Gene targeting in the brain, Imaging techniques, Animal models, Electrophisiological approaches, (epi)genetic approaches, human, Cytokines, Microglia, Astrocyte, Leukocyte, Blood-Brain Barrier

Call topic

Neuroinflammation

Proposed runtime

2014 - 2018

Project team

Audinat (Coordinator)
France (ANR)
Steinhäuser
Germany (BMBF)
Kirchhoff
Germany (BMBF)
de Curtis
Italy (MOH)