WP 3 | Inflammation in affecting brain function

Objectives

O3.1 Identification of the mechanisms of microglia activation in epilepsy
O3.2 Analysis of the role of microRNAs in epilepsy
O3.3 Analysis of the blood-brain barrier (BBB) as entry route for peripheral immune cells into the brain

WP3 aims to understand how brain inflammation contributes to pathogenic events that result in epilepsy, focusing on the role of astrocytes and microglial cells as well as of peripheral immune cells entering the brain via the BBB. WP3 will investigate inflammation in the various phases of epilepsy, during initiation, the latent period, the chronic phase and during the establishment of secondarily generalized seizures. The consequences of glia cell dysfunction or immune cell invasion will be investigated in post-epilepsy surgery patient specimens and in epilepsy animal models associated or not-associated to an inflammatory cofactor. In parallel, the role of microRNAs will be evaluated. WP3 will also include experiments on the human tissue to study the role of seizure activity in the generation of gliosis and the expression of inflammatory markers. It will be done in a large number of post-surgical samples (>100) from temporal lobe epilepsies and focal cortical displasias. WP3 will lead to a better knowledge of the fundamental mechanisms of neuroinflammation in the pathogenesis of focal epilepsy by identifying new inflammatory biomarkers and glial targets which will improve the diagnosis and treatment of epilepsies.

Tasks (and involved participants)

T3.1 Analysis of seizure dependent microglia activation and scar formation (INSERM)
T3.2 Evaluation of cytokines and their receptors in interactions of microglia, astrocytes and neurons (UKB, FINCB)
T3.3 Analysis of microRNAs in seizure-dependent glia activation (AMC)
T3.4 Analysis of BBB dysfunction in seizure-dependent immune responses (INSERM, FINCB)

Deliverables

D3.1 Molecular identification of microglia and astrocyte activation signals in epilepsy (Mo 36);
D3.2 Parameters of microglial and astroglial responses in vivo in epileptic mice (Mo 48);
D3.3 Definition of BBB function in seizure-dependent immune responses (Mo36