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INSPIE
FunderFrench National Research Agency (ANR)
Funder Contribution €516,285.00
DurationFrom 01 Oct 2021
Project codeANR-21-CE17-0019
Open Access mandatePublications: NoResearch data: No
Identifiers
Description
Hypoxia-ischemia (HI) is one of the leading causes of neurodevelopmental morbidities in infants. There are no pharmacological treatments. HI brain injury is characterized by inflammatory response along with alterations in the blood-brain barrier (BBB), both triggering neuronal damage. INSPIE project will explore purine derivatives drugs (PDD), acting through GSK-3ß and prohibitin (PHB) pathways. Our results suggest that PHB prevents mitochondrial permeabilisation, apoptosis in both neurons and the vascular bed. We showed that PDD are neuroprotective effects in HI-neonatal rats. The project will evaluate key aspects of PDD: 1) Describe the neuroprotective effects of PDD303 in the Rice-Vannucci model and to elucidate mechanism (s) of actions; 2) Establish behavioral outcomes and long-term neuroprotective effects; 3) effects on human BBB model and 3D human organoids for translational studies. INSPIE project may provide a new therapeutic option on the treatment of brain injury in neonate.
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Hypoxia-ischemia (HI) is one of the leading causes of neurodevelopmental morbidities in infants. There are no pharmacological treatments. HI brain injury is characterized by inflammatory response along with alterations in the blood-brain barrier (BBB), both triggering neuronal damage. INSPIE project will explore purine derivatives drugs (PDD), acting through GSK-3ß and prohibitin (PHB) pathways. Our results suggest that PHB prevents mitochondrial permeabilisation, apoptosis in both neurons and the vascular bed. We showed that PDD are neuroprotective effects in HI-neonatal rats. The project will evaluate key aspects of PDD: 1) Describe the neuroprotective effects of PDD303 in the Rice-Vannucci model and to elucidate mechanism (s) of actions; 2) Establish behavioral outcomes and long-term neuroprotective effects; 3) effects on human BBB model and 3D human organoids for translational studies. INSPIE project may provide a new therapeutic option on the treatment of brain injury in neonate.
