NEURODEVELOPMENTAL DISORDERS

N/A

Rodent models of encephalopathy of prematurity for the search for therapeutic targets and for the screening of therapeutic agents

Rodent models of encephalopathy of prematurity

- Models suitable for therapeutic research targeting neuroinflammation (induced by systemic inflammation produced by IL-1beta, IL-6, TNF-alpha, LPS, or Poly:IC).
- Models suitable for functional studies and long-term consequences (double hit and predisposing factor for brain pathology in adulthood).

Analysis tools: identification of cellular and molecular mechanisms and therapeutic efficacy measures

- Temporal monitoring of cell phenotyping: IF with quantification, RNAscope, FACS for immune and brain cells, including phagocytosis of synaptic markers (http://www.neuroinflammation.fr/index.html#microglie).
- Temporal monitoring of the blood-brain barrier (IF, qRT-PCR, dextrans, octreotide).
- Identification of molecular mechanisms: qRT-PCR and RNA-seq on cell populations sorted by MACS, scRNA-seq, spatial transcriptomics by Visium technology.
- Analysis of motor and cognitive behaviour, social interactions (Live Mouse Tracker) and aggressiveness, and of energy metabolism during development (https://neophen.org) and in adulthood.
- Analysis of functional brain connectivity by functional ultrasound brain imaging (fUS) (Iconeus One system; collaboration with Mickael Tanter, ESPCI, Institut Langevin, Paris, France).

Pediatric head injury rodent models for therapeutic target discovery and screening of therapeutic agents

Pediatric head injury rodent model

- Models suitable for research of therapeutics targeting head injury-induced neuroinflammation (closed-skull drop) during the neurodevelopmental period (systemic inflammation produced by IL-1beta, IL-6, TNF-alpha, LPS, or Poly:IC)
- Models suitable for functional studies and remote (other brain structures) and long-term (tertiary phase) consequences.


Analysis tools: identification of cellular and molecular mechanisms and therapeutic efficacy measurements

- Temporal monitoring of cell phenotyping: IF with quantification, RNAscope, FACS for immune and brain cells, including phagocytosis of synaptic markers (http://www.neuroinflammation.fr/index.html#microglie).
- Temporal monitoring of the blood-brain barrier (IF, qRT-PCR, dextrans, octreotide).
- Identification of molecular mechanisms: qRT-PCR and RNA-seq on cell populations sorted by MACS, scRNA-seq, spatial transcriptomics by Visium technology.
- Analysis of motor and cognitive behaviour, social interactions (Live Mouse Tracker) and aggressiveness, and of energy metabolism during development (https://neophen.org) and in adulthood.
- Analysis of functional brain connectivity by functional ultrasound brain imaging (fUS) (Iconeus One system; collaboration with Mickael Tanter, ESPCI, Institut Langevin, Paris, France)

Phase 2 and 3 clinical trials on cohorts of patients with neurodevelopmental diseases

Pediatric CIC of the Robert Debré Hospital
Biological Resource Centre, including brain tissue
Different neonatal and paediatric cohorts clinically phenotyped, and genotyped for some of them

Tools
- 3T MRI with the possibility of DTI, morphometry and perfusion imaging
- High definition EEG
- Blood immune phenotyping (FACS, Luminex, ROS production)
- RNAseq, metabolomics on blood and urine