CEREBROVASCULAR MECHANISMS OF BRAIN DISORDERS
Department : Neurosciences - Research axis : Translational biology
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.
Team
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Nicola Marchi
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Staff | |
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Marine Blaquière
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Badreddine Boussadia
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Vincent Costalat
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Philippe Coubes
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Arielle Crespel
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Cyril Dargazanli
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Wendy Klement
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Mireille Lerner-Natoli
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Marie-Christine Picot
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Emma Zub
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Frederic de Bock
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Major publications
Total of 65 pubblications. Scopus h-index: 31
https://www.scopus.com/authid/detail.uri?authorId=6603811210
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.