CEREBROVASCULAR AND GLIA RESEARCH
Department : Neuroscience
Research subject
We study neurovascular unit cells in central nervous system (CNS) disease settings. By using a translational research approach, we investigate how reactivity or plasticity of glia-pericyte structures and blood-brain barrier permeability contribute to neuro-inflammation, compounding to pathological neuronal modifications. We integrate in vivo, in vitro laboratory and clinical approaches to discover pharmacological entry-points and biomarkers of CNS diseases that are contingent to neurovascular unit dysfunction.
Research axis 1: Glio-vascular cell reactivity in experimental and human temporal lobe epilepsy: pro- and anti-inflammatory mechanisms. New anti-seizure solutions are required to modify the progression or to reduce the severity of seizures. This is germane to instances where seizures cannot be sufficiently controlled by using anti-epileptic drugs or when, irrespective from drug responsiveness, side effects need to be avoided. We combine cellular-level tools, in vivo animal models and surgically resected human brain specimens to understand the role of glia reactivity and blood-brain barrier damage in the pathophysiology of epilepsy. The current projects focus on the AnnexinA1-GR endogenous anti-inflammatory pathway and TNF inflammation in human and experimental epilepsy and aim at identifying new pathways to limit seizure pathophysiology and activity.
Research axis 2: Environmental contaminants as promoters of neuro-inflammation and neuro-vascular damage. The impact of dietary and continuous exposure to environmental contaminants on neuro-glio-vascular structures and cells is entirely unknown. We study the impact of long term exposure of pesticide cocktail and glyphosate at realistic doses on the CNS functions and peripheral organs. As perinatal inflammation, which is primarily dependent on the reactivity of glial and vascular cells, is a risk factor for the development of neurological and psychiatric disorders, one important aspect of our project is to evaluate the consequences of contaminant exposure during embryonic and postnatal development on glia and cerebrovascular cells.
Clinical Research: Mechanisms of neurovascular damage and inflammation post-stroke. We investigate local and systemic inflammatory or biomarker signatures in post-ischemic stroke using cardio-embolic and atherosclerotic human clots and blood samples.
Collaborations: IGF or CHU Montpellier (P. Courtet, C Jopling, P. Marin, J Perroy, F. Rassendren), INRA Toxalim Toulouse (L Payrastre, L. Lakhal), ENS Paris (S Garel), La Timone CHU, Marseille (F Bartolomei), GIN and CHU Grenoble (E Barbier, A Depaulis), University of South Wales, UK (D. Bailey), University of Bonn (C Steinhauser), University of Saarland (F Kirchhoff), Besta Neurological Hospital Milan, Italy (M De Curtis, R. Garbelli); Mario Negri Research Institute, Milan, Italy (A. Vezzani), Case Western Reserve University and FloTBI, USA (D Janigro), Rochester Institute of Technology, USA (T Gaborski), Cleveland Clinic, USA (C. Ghosh).
Funding: ANR, FRC, iMUSE (University of Montpellier), ANSES, MSCA-ITN EU-GliaPhD, ERANET Neuro-Vasc, Fondation de France
Team
Major publications
Total of 65 pubblications. Scopus h-index: 31
https://www.scopus.com/authid/detail.uri?authorId=6603811210
RECENT PUBLICATIONS:
- Zub E, Canet G, Garbelli R, Blaquiere M, Rossini L, Pastori C, Sheikh M, Reutelingsperger C, Klement W, de Bock F, Audinat E, Givalois L, Solito E, Marchi N (2019) The GR-ANXA1 pathway is a pathological player and a candidate target in epilepsy. FASEB J. Oct 16:fj201901596R. doi: 10.1096/fj.201901596R
lien pubmed - Klement W, Blaquiere M, Zub E, deBock F, Boux F, Barbier E, Audinat E, Lerner-Natoli M, Marchi N (2019). A pericyte-glia scarring develops at the leaky capillaries in the hippocampus during seizure activity. Epilepsia, Jul;60(7).
lien pubmed - Thion MS*, Mosser CA*, Ferezou I, Grisel P, Baptista S, Low D, Ginhoux F, Garel S*, Audinat E* (*equal contribution; 2019) Biphasic impact of prenatal inflammation and microglia depletion on the wiring of neocortical inhibitory circuits. Cell Rep, 28(5):1119-1126.e4.
lien pubmed - Nikolic L, Shen W, Nobili P, Virenque A, Ulmann L, Audinat E (2018) Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis. Glia 66:2673–2683.
lien pubmed - Klement W, Garbelli R, Zub E, Rossini L, Tassi L, Girard B, Blaquiere M, Bertaso F, Perroy J, de Bock F, Marchi N (2018) Seizure progression and inflammatory mediators promote pericytosis and pericyte-microglia clustering at the cerebrovasculature. Neurobiol Dis 113:70–8.
lien pubmed