Microvascular Endothelium and Neonate Brain Lesions

Region-Inserm Team NeoVasc (ERI28)

Research team



Dr Bruno Gonzalez
Laboratoire "NeoVasc" , Microvascular Endothelium and Neonate Brain Lesions
Region-Inserm Team - ERI28
IRIB - Institute for Research and Innovation in Biomedicine
Bâtiment Recherche
Faculté de Médecine Pharmacie
22 Boulevard Gambetta

Research interest:

The research topic of the “NeoVasc"Team 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 neuro-psychiatric 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, even if recent clinical data strongly suggest that the use of magnesium sulphate 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 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 several data that revealed a major contribution of the brain microvessels in the neuronal development, the role of the brain vasculature in neonatal brain lesions is, so far, poorly investigated. Considering all these elements, the domain of research of ERI 28 « NeoVasc » is focused on a single thematic: The cerebral perinatal handicap and on a single problematic: The contribution of the brain microvasculature to the development of neonatal brain lesions In order to complete this project of research, ERI28 « NeoVasc » has 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 to adapt them to the clinical research. List of main publications from 2012 Roux C, Lesueur C, Aligny C, Brasse-Lagnel C, Genty D, Marret S, Laquerrière A, Bekri S, Gonzalez BJ. 3MA inhibits autophagy and favours long-term integration of grafted Gad67-GFP GABAergic precursors in the developing neocortex by preventing apoptosis. Cell Transplantation, 2013, in press. Omouendze PL, Henry V, Porte B, Dupré N, Carmeliet P, Gonzalez BJ, Marret S, Leroux P. Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator dependent gelatinase activation in mice neonate brain microvessels. PLos One 2013, in press. Henry VJ, Lecointre M, Laudenbach V, Ali C, Macrez R, Jullienne A, Berezowski V, Carmeliet P, Vivien D, Marret S, Gonzalez BJ, Leroux P. High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate. Neurobiol Dis. 2013, 50:201-8. Mura T, Picaud JC, Larroque B, Galtier F, Marret S, Roze JC, Truffert P, Kuhn P, Fresson J, Thiriez G, Arnaud C, Mercier G, Picot MC, Ancel PY, Ledesert B; Etude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE) Study Group. Cognitive Impairment at Age 5 Years in Very Preterm Infants Born Following Premature Rupture of Membranes. J Pediatr. 2013, in press. S. Marret, L.Marchand-Martin, JC Picaud, JM Hascoët, C Arnaud, JC Rozé, P Truffert, B Larroque, M. Kaminski, P-Y.Ancel for the EPIPAGE Study Group. Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: The EPIPAGE cohort study. PLos One 2013, 8:e62683. Jégou S, El Ghazi F, de Lendeu PK, Marret S, Laudenbach V, Uguen A, Marcorelles P, Roy V, Laquerrière A, Gonzalez BJ. Prenatal alcohol exposure affects vasculature development in the neonatal brain. Ann Neurol. 2012; 72:952-960. 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, Gonzalez BJ. NO-dependent protective effect of VEGF against excitotoxicity on layer VI of the developing cerebral cortex. Neurobiol Dis. 2012; 45:871-886. Charkaluk ML, Marchand-Martin L, Ego A, Zeitlin J, Arnaud C, Burguet A, Marret S, Rozé JC, Vieux R, Kaminski M, Ancel PY, Pierrat V; Epipage Study Group. The influence of fetal growth reference standards on assessment of cognitive and academic outcomes of very preterm children. J Pediatr. 2012;161:1053-1058.

Figure legend: Visualization of a Gad67-GFP grafted neuron in the host cortex 15 days after the transplantation. The grafted cell is immunoreactive for GAT1 puncta (red signal). Roux et al., Cell Transplantation, 2013 in press.

Key words: Cerebral palsy - prematurity - excitotoxicity - neuroprotection
Conçu par Alexis Lebon © 2017 - Tous droits réservés.