« The preterm brain : state of the art »

During the last few years notable progress has been made in the understanding of the mechanism controlling the development of the brain. These new discoveries have given us fascinating new perspectives on and enhanced comprehension of lesions that could affect the brain of the foetus or the newborn, and specifically the premature newborn. The latter remains at high risk of developing cerebral problems.

The development of innovative strategies for protecting the brain of the foetus and newborn inevitably depends on our capacity to analyse more effectively the macroscopic, microscopic and molecular events causing these cerebral lesions.These scientific and medical advances in the understanding of the existence and prevention of lesions of the immature brain involve various fields such as the biology of inflammation and neural death, the pharmacology of neuro-protective agents, stem cells, ultrasonic and magnetic resonance imagery, recording electrical cerebral activity through electroencephalograms, the development of cognitive function, and also the mechanism of pain.

Resarch Unit U676 – University Paris-Diderot
Director : Pierre Gressens

Our laboratory is dedicated to the pathophysiology, functional consequences and neuroprotection of lesions of the developing brain. Three major themes are being developped.

• "Perinatal brain": neurological handicap of perinatal origin remains a public health problem the incidence of which has been shown to increase in industrialized countries.
• "Mitochondrial disorders": This project aims at designing therapies for mitochondrial disorders through a better understanding of the underlying mechanisms. Different models are being used including the Harlequin mouse, tumorigenesis induced bysuccinate dehydrogenase deficiency, cellular models of Friedreich ataxia.
• "Neuronal excitability": In epilepsy, a major hypotheis is thata there is an inbalance between exitatory and inhibitory systems, although the precise underlying molecular mechanisms are not totally understood. Dendritic changes havve been implicated. In the present project, we study the impact of an intrinsic factor (CDP/Cux1) and of an extrinsic factor (sst2 somatostatinergic receptor) on dendrite morphogenesis.

By promoting the interaction between molecular biologists, developmental neurobiologists, cognitivists, physiologists, pharmacologists, radiologists and clinicians, this program should permit a better understanding of the multifactorial pathophysiology of perinatal brain lesions and mitochondrial disorders, and, accordingly, to propose new strategies for a targeted and original neuroprotection. Our strategy based on concepts and methodologies of developmental neurobiology will allow to i) introduce in perinatology new conceptual tools permitting a more integrated approach of the fetus and newborn at risk to develop brain lesions, and ii) to offer to the clinician new preventive and/or therapeutic strategies which can be tested in controlled clinical trials in neonates at risk to develop brain lesions or in pediatric patients with mitochondrial disorders. The localization of our group within a pediatric hospital will also allow clinicians from different services to integrate a research structure.