Our Pillars of Fundamental Research

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At Neurochlore, research has always been at the heart of our mission. Until 2022, our work explored the fundamental mechanisms of brain development, with a clear goal: to understand how the brain is formed during pregnancy and in the early years of life. This critical period shapes an individual’s future and can be the starting point for certain neurodevelopmental disorders.
Through a rigorous scientific approach, we have identified key processes and explored the alterations that may lead to these disorders. Our research has laid the foundation for new perspectives and continues to inspire our innovations within B&A Oncomedical and B&A Biomedical.

Brain development is a fascinating process that begins in the early embryonic stages and continues well after birth. During this critical period, a series of events, orchestrated at different scales, shapes the brain’s architecture: neuronal proliferation and migration, circuit maturation, establishment of synaptic connections… A true biological symphony that structures the foundations of cognitive and behavioral functioning.

However, this period is also one of extreme vulnerability. Genetic or environmental disruptions can alter these mechanisms and have a lasting impact on brain maturation. These alterations lie at the heart of neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD).
Understanding these modifications and their consequences is a key challenge in order to anticipate and, ultimately, propose intervention strategies.

The concept of Neuro-archaeology is based on a key idea: certain neurological and psychiatric disorders, such as childhood epilepsy, Autism Spectrum Disorders (ASD), or genetic diseases, result from early pathological events (genetic mutations, environmental exposures, etc.) that alter the developmental process. These alterations, occurring in utero or during the perinatal period, affect brain maturation and leave a lasting imprint on brain development.
Introduced in 2008 by Yehezkel Ben-Ari, this concept suggests that certain neurons remain “immature,” generating abnormal activities that disrupt brain function and become the driving force behind the pathology. Identifying agents capable of specifically blocking these immature neuronal activities thus paves the way for new therapeutic strategies.

Pregnancy and delivery are key stages in development, marked by high biological complexity and increased vulnerability to environmental factors such as endocrine disruptors or pollution. During birth, a cascade of physiological events is triggered to prepare the body for life outside the womb. Among these, the release of stress molecules promotes the activation of the respiratory system, while oxytocin, a hormone essential for contractions, plays a neuroprotective and analgesic role for the fetus. Our research, conducted on animal models, has explored the changes that occur during this critical period, particularly the impact of prematurity and cesarean sections on brain development.

In the adult brain, GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter, promoting the influx of chloride ions into neurons, where the chloride concentration is low. In contrast, in immature neurons, where the chloride concentration is high, GABA produces an excitatory effect. This phenomenon, observed in all animal species, is crucial for brain maturation.
Under physiological conditions, the intracellular chloride concentration gradually decreases during development, allowing GABA to switch from excitatory to inhibitory. This transition is primarily regulated by NKCC1, a chloride ion importer. However, in many pathologies, excessive activity of NKCC1 maintains an immature neuronal state, illustrating the concept of Neuro-archaeology.
Our therapeutic research focuses on blocking these immature neuronal activities using agents like Bumetanide, an NKCC1 inhibitor. By restoring a normal chloride level, this treatment could rebalance GABA function and alleviate symptoms associated with related pathologies.