Team Nicola MARCHI – Étienne AUDINAT

Cerebrovascular and Glia Research

Etienne Audinat
DR1, CNRS
Nicola Marchi
CRHC, CNRS

We investigate cells at the neurovascular interface in the context of central nervous system diseases. Through translational research, we explore how the responsiveness and adaptability of neurovascular cells, as well as the permeability of the blood–brain barrier, influence neuroinflammation and contribute to progressive alterations in neuronal function. We conduct clinical studies on peripheral–CNS immune cross-talk. Our approach integrates in vivo and in vitro experimental models with clinical investigations to elucidate underlying mechanisms and identify peripheral blood biomarkers associated with neurovascular unit dysfunction and neurological outcomes.

Glio-vascular cell reactivity in experimental and human focal and genetic epilepsies. This framework is relevant for cases where seizures cannot be adequately controlled with anti-seizure medications or where, regardless of drug responsiveness, side effects must be minimized. We integrate cellular-level and neurophysiological tools, in vitro and preclinical models (including status epilepticus, temporal lobe epilepsy, and Dravet syndrome), and the analysis of surgically resected human brain tissue to investigate the role of glial cell reactivity and blood-brain barrier damage in the pathophysiology of these seizure conditions. We explore opportunities for novel targets and the discovery of blood or imaging biomarkers to improve patient management. Our research also examines the contribution of seizures to neurological deficits and neurodegeneration in the aging population.

Neurovascular damage and immune communications in human stroke. The goal of our research is to identify specific molecular and biomarker signatures that can inform the development of add-on therapeutic options, which would target key inflammatory pathways in conjunction with mechanical thrombectomy. By focusing on these inflammatory pathways, we aim to not only enhance the effectiveness of mechanical thrombectomy but also reduce the risk of post-procedural complications and improve patient outcomes. Our clinical team leverages mechanical thrombectomy procedures to obtain intracranial clot and peri-clot blood samples. These samples are analyzed to characterize the inflammatory milieu within the affected tissue and surrounding vasculature. This enables us to improve our understanding of the molecular et cellular mechanisms involved.

Environmental contaminants and xenobiotics at brain borders: risk factors of neuro-inflammation and neuro-vascular frailty. The impact of exposure to environmental pollutants or xenobiotics on neuro-glio-vascular structures and cells remains unclear. We investigate the effects of long-term, age-related exposure to contaminants at realistic doses on CNS functions and peripheral organs. Given that perinatal inflammation, primarily driven by the reactivity of glial and vascular cells, is a known risk factor for the development of neurological and psychiatric disorders, a critical aspect of our project is to evaluate the consequences of contaminant exposure (pesticides, bisphenol and others) during embryonic and postnatal development on glia and cerebrovascular cells in adulthood.

The Neurovascular Unit: A Nexus in CNS Diseases and Maladaptation. At the NVU, the blood-brain barrier (BBB) consists of a tight endothelial-pericyte-astrocyte end-feet assembly. In response to acute insults or chronic conditions (peripheral or brain), BBB permeability increases with pericyte and glial cell reactivity. These events contribute to a loss of parenchymal homeostasis and facilitate aberrant synaptic transmission, thereby representing a risk factor for negative neurological sequelae and brain frailty.

Team leader
Etienne
Audinat
DR1, CNRS
  IGF Sud 215
  04 34 35 92 09
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Nicola
Marchi
CRHC, CNRS
  IGF Sud 118
  04 34 35 92 20
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Researchers
Vincent
Costalat
PU-PH1, UM
  IGF Nord 013
  04 11 75 96 80
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Cyril
Dargazanli
PH, CHU
  IGF Sud 118
  04 34 35 92 20
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Technicians and engineers
Marine
Blaquière
TCN, UM
  IGF Sud 118
  04 34 35 92 20
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Postdoctoral researchers and doctoral students
Jeremias
Chousidis
Chercheur CDD, CNRS
  IGF Sud 113
  04 34 35 92 20
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Noémie
Cresto
Chercheur CDD, CNRS
  IGF Sud 118
  04 34 35 92 20
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Athénaïs
Genin
Doctorant(e), Inserm
  IGF Sud 118
  04 34 35 92 20
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Fixed term contract technicians and engineers
Alicia
Janvier
IE CDD, Inserm
  IGF Sud 118
  04 34 35 92 20
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Tristan
Moujellil Legagneur
IE CDD, Inserm
  IGF Sud 118
  04 34 35 92 20
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Paola
Nobili
IR CDD, Inserm
  IGF Sud 116
  04 34 35 92 85
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Frédéric
Nouguier-Morin
IE CDD, UM
  IGF Sud 118
  04 34 35 92 20
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Nathalie
Reichert
IE CDD, Inserm
  IGF Sud 215
  04 34 35 92 09
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  • Janvier A, Cresto N, Nistreanu C, Genin A, Mathias M, Vitalis M, Fabene P, Parrella E, Zussy C, Audinat E, Givalois L, Marchi N. Neurophysiological and neuroinflammatory adaptations to seizure activity in aging. Neurobiol Dis. 2025 in press.
  • Lengvenyte A, Blaquiere M, Dubois J, Bonnin M, Bourret J, Hamzeh-Cognasse H, Olié E, Cognasse F, Marchi N#, Courtet P#. Integrating cellular and soluble immune signatures of major depression with and without recent suicide attempts. Transl Psychiatry. 2025 Oct 6;15(1):377. doi: 10.1038/s41398-025-03601-2. PMID: 41053103
  • Chousidis I, Ellero-Simatos S, Payrastre L, Payros G, Lippi Y, Blaquière M, Faucherre A, Drouard A, Jopling C#, Torrente AG#, Marchi N#. Bisphenol analogue exposure at low concentrations modifies heart-brain functions and transcriptomics in zebrafish larvae. J Hazard Mater. 2025 Sep 29;498:140004. doi: 10.1016/j.jhazmat.2025.140004. PMID: 41045584
  • Rapido F, Marchi N#, Labreuche J, Ter Schiphorst A, Blaquière M, de Bock F, Calcado V, Fendeleur J, Marin P, Perrigault PF, Moynier M, Chanques G, Costalat V#, Dargazanli C#. Acute ischemic stroke and reperfusion drive molecular immune-vascular activations detectable in peripheral blood.
    J Neurointerv Surg. 2025 Sep 23:jnis-2025-023885. doi: 10.1136/jnis-2025-023885. PMID: 40987590
  • Cresto N, Givalois L, Badaut J, Janvier A, Genin A, Audinat E, Brewster AL, Marchi N. Bursts of brain erosion: Seizures and age-dependent neurological vulnerability. Trends Mol Med. , 2025, Jun;31(6):535-547. doi: 10.1016/j.molmed.2024.11.003. PMID: 39665957
  • Pinzon-Hoyos N, Li Y, McGee M, Poolos NP, Marchi N, Brewster AL. Drug-resistant epilepsy associated with peripheral complement decreases and sex-specific cytokine imbalances: a pilot study. Sci Rep. 2025 Feb 11;15(1):5096. doi: 10.1038/s41598-025-88654-5. PMID: 39934240
  • Dargazanli C#, Blaquière M, Moynier M, de Bock F, Labreuche J, Ter Schiphorst A, Derraz I, Radu RA, Gascou G, Lefevre PH, Rapido F, Fendeleur J, Arquizan C, Bourcier R, Marin P, Machi P, Cagnazzo F, Hirtz C, Costalat V#, Marchi N#. Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke. J Neurointerv Surg 2025 Jan 17;17(2):159-166. doi: 10.1136/jnis-2023-021365. PMID: 38514190
  • Costalat V. et al. Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size. N Engl J Med 2024 May 9;390(18):1677-1689. doi: 10.1056/NEJMoa2314063. PMID: 38718358
  • Cresto N, Courret M, Génin A, Martin CMP, Bourret J, Sakkaki S, de Bock F, Janvier A, Polizzi A, Payrastre L, Ellero-Simatos S, Audinat E, Perroy J, Marchi N. Continuous low-level dietary exposure to glyphosate elicits dose and sex-dependent synaptic and microglial adaptations in the rodent brain. Environ Pollut. 2024 Mar 15;345:123477. doi: 10.1016/j.envpol.2024.123477. PMID: 38307239
  • Garcia V*, Blaquiere M*, Janvier A, Cresto N, Lana C, Genin A, Hirbec H, Audinat E, Faucherre A, Barbier EL, Hamelin S, Kahane P, Jopling C, Marchi PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions. Neurobiol Dis. 2023 Oct 15;187:106297. doi: 10.1016/j.nbd.2023.106297. PMID: 37717661

Mechanisms of neurovascular damage and inflammation due to large vessel occlusion (V. Costalat, C. Dargazanli, A. Ter-Schiphorst, F. Cagnazzo, E. LeBars, CHU Montpellier/IGF). We investigate brain and systemic inflammatory or biomarker signatures in post-ischemic stroke using cardio-embolic and atherosclerotic human clots and intracranial blood samples. We aim to improve patient management and offer add-on therapeutic option along with mechanical thrombectomy. We study mechanisms of idiopathic intracranial hyper- or hypo-tension. Find out more

Analysis of explanted intracranial electrodes in drug-resistant epilepsy as a source of intracranial biological traces (Prof. Bartolomei, J. Scholly, S. Lagarde, CHU La Timone, Marseille). The goal is to isolate a nano-scale quantity of RNA or protein derived from the intracranial tissue environment where the depth electrode resided during the pre-surgical exploration of seizure networks. To overlap these innovative biological data with those obtained by imaging and SEEG to establish a map of the molecular physiological connections in the epileptic brain. Find out more

Neurovascular damage and inflammatory cross-talk in psychiatric conditions: focus on depression and suicide attempts (P. Courtet, E. Olie, R. Belzeaux; CHU/IGF). The goal is to discover outcome protein biomarkers in blood and to develop an add-on therapeutic option based on the modulation of specific inflammatory players.

  • Garel (ENS Paris), N. Rouach (Collège de France, Paris) : Microglia in the wiring of Inhibitory circuits during sensory cortex critical periods (MicroSenso) ; ANR-19-CE16-0018
  • Rassendren and P. Mollard teams (IGF) : Deciphering ATP Signaling in Epilepsy with Biosensors (Diapason) ;  ANR-20-CE16-0003.
  • Levi (IFM, Paris), D. Blum (Lille Neuroscience & Cognition), C. Bernard (INS Marseille) : The Janus-faced Impact of caffeine in the developing and the ageing brain: role of synaptic remodeling (JANUS) ; ANR-21-CE14-0053.
  • Hirbec (Rassendren team, IGF), G. Dorothée (Saint Antoine Research Center, Paris), V. Navarro (Salpêtrière Hospital & Paris Brain Institute, Paris) : tRreg protection of seizure propagation zones In temPoral Lobe EpilepsY (RIPLEY) ; ANR-23-CE14-0052.
  • Tronche (Neuroscience Paris Seine), D. Blum (Lille Neuroscience & Cognition) : Stress signaling in microglia: behavioral, functional, and molecular consequences (MicroGlioStress) : ANR-23-CE14-0010.
  • Collaboration with J. Perroy (IGF), ANR-Glyphore: impact of dietary glyphosate on brain functions.
  • Collaboration with C. Jopling (IGF), ANSES OptoFish: examines the impact of environmental contaminats using zebrafish models.