MÉCANISMES VASCULAIRES DES MALADIES NEUROLOGIQUES
Département : Neuroscience - Axe de recherche : Biologie Translationnelle

Thème de recherche

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. 


Équipe

Chef d'équipe

Nicola Marchi
CRCN, CNRS


  IGF Sud 118

  04 34 35 92 20

 

Personnel de l'équipe

Badreddine BOUSSADIA
Accueil scientifique, CNRS


  IGF Sud 118

  04 34 35 92 20

 

Marine Blaquière
TCN, UM


  IGF Sud 118

  04 34 35 92 20

 

Philippe Coubes
PU-PH, CHU


  CHU

  04 67 33 74 64

 

Arielle Crespel
PH, CHU


  CHU Montpellier

  04 34 35 92 20

 

Cyril Dargazanli
Accueil scientifique, CHU


  IGF Sud 118

  04 34 35 92 20

 

Wendy Klement
Stagiaire, Inserm


  IGF Sud 118

  04 34 35 92 20

 

Mireille Lerner-Natoli
DR2, CNRS


  IGF Sud 118

  04 34 35 92 20

 

Marie-Christine Picot
PU-PH, CHU


  CHU Montpellier

  04 67 33 89 79

 

Emma Zub
AI CDD, CNRS


  IGF Sud 225

  04 34 35 92 20

 

Frederic de Bock
IEHC, Inserm


  IGF Sud 118

  04 34 35 92 20

 


Publications majeures

Total of 65 pubblications. Scopus H-index 31

RECENT PUBLICATIONS:

1: Patrizia Giannoni, Margarita Arango-Lievano, Ines Das Neves, Marie-Claude Rousset, Kevin Barranger, Santiago Rivera, Freddy Jeanneteau, Sylvie Claeysen and Nicola Marchi. Cerebrovascular pathology during the progression of experimental Alzheimer's disease. Neurobiology of Disease, 2016 in press

2: Garbelli R, de Bock F, Medici V, Rousset MC, Villani F, Boussadia B, Arango-Lievano M, Jeanneteau F, Daneman R, Bartolomei F and Marchi N. PDGFRβ(+)cells in human and experimental neuro-vascular dysplasia and seizures.Neuroscience. 2015 Oct 15; 306:18-27

3: Milesi S, Boussadia B, Plaud C, Catteau M, Rousset MC, De Bock F, Schaeffer M, Lerner-Natoli M, Rigau V and Marchi N. Redistribution of PDGFRβ cells and NG2DsRedpericytes at the cerebrovasculature after status epilepticus. Neurobiology of Disesase, 2014 Nov; 71:151-8.

4: Marchi N, Granata T, Janigro D. Inflammatory pathways of seizure disorders. Trends Neuroscience. 2014 Feb; 37(2):55-65.

5: Boussadia B, Ghosh C, Plaud C, Pascussi JM, de Bock F, Rousset MC, Janigro D and Marchi N. Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression. Neuroscience. 2014 Oct 2;281C: 124-134.

6: Ghosh C, Hossain M, Puvenna V, Martinez-Gonzalez J, Alexopolous A, Janigro D and Marchi N. Expression and functional relevance of UGT1A4 in a cohort of human drug-resistant epileptic brains. Epilepsia. 2013 Sep; 54(9):1562-70. 

 

 

 

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