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

Thème de recherche

The Team focuses on the neuro-vascular unit (NVU) and its pharmacology. The Team investigates the pathophysiological role of cerebral vessels in contribuiting 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.
Neuro-vascular techniques used: i) in vivo video-electroencephalography and analysis of frequency signals; ii) 3D / 2D in vivo and in vitro imaging (2-photon or confocal). Fluorescent 3D brain reconstruction; iv) ex vivo electrophysiology (e.g., field potential); v) molecular biology (e.g., microvessel isolation, immunohistochemistry, western blot, RT-PCR). Models used include:  i) in vivo models of seizures or Alzheimer's Disease; ii) ex-vivo organotypic culture; iii) in vivo and ex-vivo models of neuro-vascular dysplasia; iv) brain specimens from drug resistant epileptic or Alzheimer's patients.
Collaborative effort within the IGF: i) IPAM platform and Jeanneteau Team (in vivo 2-Photon imaging and reconstruction); ii) S. Clayesen (experimental models of AD and behavioral testing); iii) Rassendren Team (model of seizures and inflammation); iv) JM. Pascussi (PXR/CAR biology).
External collaborations: C. Besta Neurologic Hospital  (Milan, Italy); Hopital La Timone (Marseille, France); INRA Toulouse (France); Cleveland Clinic (USA).
 

Foundamental-Translational Research

Funding: Federation pour la Recherche sur le Cerveau (FRC, France) – Brain and Inflammation; Citizen United Research Epilepsy (CURE, USA); Innovator Award. Role of pericytes and neuro-vascular coupling in the epileptic brain and AD progression. While loss of brain endothelial and glial cells functionality has been demonstrated to contribute to BBB mechanism of seizures, the role of cerebrovascular mural cells has been overlooked. We propose the hypothesis that pericytes inflammatory modifications are involved in the pathophysiology of seizure disorders and AD.

Funding: National Institute of Health –R01 (5 years) NIH NINDS (USA); Fondation Françoise pour la Recherché sur l'Epilepsie, FFRE TF1 (France); Fondation Françoise pour la Recherché sur l'Epilepsie, FFRE Valerie Chamaillard Award (France). Role of P450 metabolic enzyme in the diseased brain. We propose the hypothesis that the bioavailability of brain drugs is affected by P450 metabolic enzymes (CYP2C, CYP3A, etc.) expressed at the neuro-vascular unti. The role of PXR and CAR nuclear receptor is being investigated.

Clinical Reserach
Prognostic serum marker of first-to-chronic seizure conversion in a cohort of adult subjects (ClinicalTrials.gov;Grant University Hospital - CHU Nimes; coll. Eric Thouvenout). We are testing whether the extent of BBB damage at time of first cryptogenic seizure is predictive for seizure recurrence. S100B serum levels will be used as a marker of BBB damage.
Identification of serum biomarkers of drug resistance in epilepsy. (Grant University Hospital - CHU Montpellier;Arielle Crespel, Marie Christine Picot, Philippe Coubes, Philippe Gélisse, Valérie Rigau, Sylvain Lehman, Mireille Lerner-Natoli). 25-30% of epileptic subjects do not respond to available anti-seizure medications. We propose serum markers for the early diagnosis of drug resistance.

Équipe

Chef d'équipe

Nicola Marchi
CR1, CNRS


  IGF Sud 225

  04 34 35 92 20

 

Personnel de l'équipe

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 225

  04 34 35 92 20

 

Alexis Faydherbe
Master 2, Inserm


  IGF Sud 225

  04 34 35 92 20

 

Mireille Lerner-Natoli
DR2, CNRS


  IGF Sud 225

  04 34 35 92 20

 

Marie-Christine Picot
PU-PH, CHU


  CHU Montpellier

  04 67 33 89 79

 

Frederic de Bock
IEHC, Inserm


  IGF Sud 225

  04 34 35 92 20

 


Publications majeures

Total of 58 pubblications. Scopus H-index 28; Citations in 2014: 341

SELECTION OF 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. 

 

 

 

Évènements

August 2017
Lun Mar Mer Jeu Ven Sam Dim
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31