Composition

• 14 Researchers (including 3 INSERM Researchers)
• 5 Technicians (including 1 AI INSERM)
• 1 Secretary
• 1 Post-doctoral fellow, 7 PhD students, 3 Master 2 students

  Facilities

• In vivo: excitotoxic brain lesions in mice neonates, hypoxo-ischemic brain lesions in mice neonate, allografts, in vivo ready siRNA, behavioural tests
• Ex vivo: Culture of organotypic brain slices from mice neonates
• In vitro: Culture of primary neonate endothelial cells, cultures of cortical neurons
• Imaging: calcimetry, vidéomicroscopy, stereology
• Transgenic mice models (PLGF-/-, tPA-/-, PAI-/-, GadGFP, GFP-LC3)

  Activity

ERI28 “NeoVasc" is located in the Faculty of Medicine and Pharmacy of Rouen and evolves in close partnership with the Department of “Neonatal Paediatrics and Intensive Care” of the Hospital of Rouen. The research topic of ERI28 "NeoVasc" is focused on neonatal brain lesions. Indeed, these lesions which affect both preterm and term infants are frequent (2 to 2.5 cases per 1000 births) and cause motor impairments, cognitive disorders and neuropsychiatric disabilities. They are the first cause of cerebral palsy in industrialized countries. Despite marked progresses in intensive cares for infants, the prevalence of cerebral palsy remained stable and even increased since the 50s. In France, 125.000 patients suffer from cerebral palsy, whereas individuals with cognitive impairment are more difficult to assess and are estimated to be 4-5 times higher. The diagnostic and prognostic tools are missing. Actually, there is no treatment routinely available. However, recent clinical data strongly suggest that the use of magnesium sulfate during pregnancies may have a beneficial effect. Because patients with cerebral palsy require a lifelong care, these lesions represent also an important economic challenge. Indeed, a recent Danish study indicated that the cost of cares is about 850.000 euros per patient. This cost is similar to that of patients suffering from neurodegenerative diseases, most often associated with aging. Consequently, considering the medical, social and economic aspects, the development of research in this field is of considerable importance for children and their families. 

Risk factors associated with neonatal brain lesions include premature birth, hypoxic-ischemic events, haemorrhages, prenatal exposure to toxins such as alcohol and fetal infections. Although the vascular system is clearly associated with several of these risks, and despite recent data that revealed a major contribution of the brain microvessels in the neural development, the role of the brain vasculature in neonatal brain lesions is, so far, poorly investigated. 

Considering all these elements, the research domain of ERI28 « NeoVasc » is focused on a single thematic: the cerebral perinatal handicap and on a single problematic: the contribution of the brain microvasculature in the development of neonatal brain lesions. In particular, research projects of ERI28 are focused on three objectives: i) to determine the interactions between the vascular and nervous cells in a lesional context, ii) to characterize the molecular and cellular mechanisms associated with cell death in neonatal brain lesions and iii) to develop neuroprotective strategies and adapt it to the clinical research.

  Main contributions

• Demonstration of the neuroprotective effect of magnesium sulfate in rodents and clinical transposition to preterm neonates
• Demonstration of phenotypic and functional specificities of brain microvessels in neonates
• Demonstration of anti-necrotic effect of VEGF against excitotoxic brain lesions
• Demonstration of deleterious effects of some classes of anaesthetics on maturation and survival of GABAergic interneurons
• Demonstration of the involvement of t-PA on genesis of cavitary white mater lesions
• Demonstration of brain vascular defects in animal models and human neonates after prenatal alcohol exposure
• Demonstration of a preventive effect of glucocorticoïds in a murine model of white matter lesions

  Latest publications

2012

• El Ghazi F, Desfeux A, Brasse-Lagnel C, Roux C, Lesueur C, Mazur D, Remy-Jouet I, Richard V, Jégou S, Laudenbach V, Marret S, Bekri S, Prevot V and Gonzalez BJ. NO-dependent protective effect of VEGF against excitotoxicity on layer VI of the developing cerebral cortex. Neurobiol Dis 2012, 45: 871-86.
  22209711
• Henry VJ, Lecointre M, Laudenbach V, Ali C, Macrez R, Jullienne A, Beresowski V, Carmeliet P, Vivien D, Marret S, Gonzalez BJ and Leroux P. High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate. Neurobiol Dis 2012
  23103420
• Jégou S, El Ghazi F, de Lendeu PK, Marret S, Laudenbach V, Uguen A, Marcorelles P, Roy V, Laquerrière A and Gonzalez BJ. Prenatal alcohol exposure affects vasculature development in the neonatal brain. Ann Neurol 2012, 72: 952-60.
  23280843

2011

• Friocourt G, Marcorelles P, Saugier-Veber P, Quille ML, Marret S and Laquerrière A. Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly. Acta Neuropathol 2011, 121: 149-70.
  21046408

2010

• Chévrier M, Brakch N, Céline L, Genty D, Ramdani Y, Moll S, Djavaheri-Mergny M, Brasse-Lagnel C, Annie Laquerrière AL, Barbey F and Bekri S. Autophagosome maturation is impaired in Fabry disease. Autophagy 2010, 6: 589-99.
  20431343
• Desfeux A, El Ghazi F, Jégou S, Legros H, Marret S, Laudenbach V and Gonzalez BJ. Dual effect of glutamate on GABAergic interneuron survival during cerebral cortex development in mice neonates. Cereb Cortex 2010, 20: 1092-108.
  19759125

2009

• Doyle LW, Crowther CA, Middleton P, Marret S and Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009: CD004661.
  19160238
• Legros H, Launay S, Roussel BD, Marcou-Labarre A, Calbo S, Catteau J, Leroux P, Boyer O, Ali C, Marret S, Vivien D and Laudenbach V. Newborn- and adult-derived brain microvascular endothelial cells show age-related differences in phenotype and glutamate-evoked protease release. J Cereb Blood Flow Metab 2009, 29: 1146-58.
  19367295

2008

• Larroque B, Ancel PY, Marret S, Marchand L, André M, Arnaud C, Pierrat V, Rozé JC, Messer J, Thiriez G, Burguet A, Picaud JC, Bréart G and Kaminski M; EPIPAGE Study group. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet 2008, 371: 813-20.
  18328928
• Zhokhov SS, Desfeux A, Aubert N, Falluel-Morel A, Fournier A, Laudenbach V, Vaudry H and Gonzalez BJ. Bax siRNA promotes survival of cultured and allografted granule cell precursors through blockade of caspase-3 cleavage. Cell Death Differ 2008, 15: 1042-53.
  18323863