Research subject

The Team focuses on the neuro-vascular unit (NVU) in vivo, blood-brain barrier (BBB) in vitro modeling and pharmacology. The Team investigates the pathophysiological role of cerebral vessels in contributing to neuronal dysfunction. The cerebrovascular tree has rheological, immunological and transport-metabolic functions, strictly controlling neuronal activity. Cerebral vessels include endothelial cells enclosed by a perivascular basal lamina, astrocytic end-feet and mural cells (pericytes and smooth muscle cells). Techniques used: i) in vivo brain microsurgery, video-electroencephalography and analysis of frequency signals; ii) 3D / 2D in vivo and in vitro NVU imaging. iii) In vitro modeling of the BBB using static and flow-based co-culture systems; iv) ex vivo electrophysiology; v) molecular biology (e.g., microvessel isolation, immunohistochemistry, western blot, RT-PCR). Moreover: i) in vivo models of epileptogenesis and spontaneous seizures; ii) ex-vivo organotypic hippocampal culture; iii) in vivo and ex-vivo models of neuro-vascular dysplasia; iv) brain specimens from drug resistant epileptic or Alzheimer's patients. Collaboration at IGF: i) IPAM platform (in vivo 2-Photon imaging and reconstruction); ii) Perroy Team (3D slice imagining); iii) JM. Pascussi (PXR/CAR biology); iv) S. Clayesen (experimental models of AD). External: Grenoble Institute of Neuroscience (GIN, France); INRA Toxalim Toulouse (France); C. Besta Neurologic Hospital  (Milan, Italy); Hopital La Timone (Marseille, France); Cleveland Clinic (USA); University of South Wales (Prof. Bailey).

Translational Research

Role of pericytes and neuro-vascular modifications in the epileptic brain and AD progression. Funding: ANR-Epicyte (MARCHI PI-coordinator), Federation pour la Recherche sur le Cerveau– Brain and Inflammation (FRC, France; PI); Citizen United Research Epilepsy, Innovator Award (CURE, USA; PI). 

Role of endocrine disruptors and pesticide cocktails on neuro-vascular structures and neuro-inflammation. Research effort coordinated with Toxalim-INRA, Toulouse, France Funding: ANR-HepatoBrain (MARCHI PI-coordinator).

Role of P450 metabolic enzyme in the diseased brain. The bioavailability of brain drugs is affected by P450 metabolic enzymes expressed at the neuro-vascular unit. The role of PXR and CAR nuclear receptors is investigated. Funding: National Institute of Health –R01 (MARCHI mPI) NIH NINDS (USA); Fondation Françoise pour la Recherché sur l'Epilepsie (FFRE-TF1; PI)

Clinical Research

Multimodal investigation of clot origin. Mechanisms of stroke / clot-induced BBB damage. Funding: Stryker Private Contract-Grant (Costalat/Marchi).  

Prognostic serum marker of first-to-chronic seizure conversion in a cohort of adult subjects (ClinicalTrials.gov; Funding Grant University Hospital - CHU Nimes; Thouvenout/Marchi). Extent of BBB damage after a first cryptogenic seizure and predictive value for seizure recurrence.