In the framework of a collaboration agreement between EBRI and the Paediatric Hospital Bambino Gesù (OPBG) in Rome, a joint laboratory has been established at the S. Paolo OPBG premises. The EBRI-OPBG joint laboratory, which was made possible also thanks to a donation from the Sacchetti Foundation, will study, using a cutting-edge technique, brain tissues removed from young patients during surgery for drug-resistant forms of epilepsy, to better understand the underlying mechanisms and to identify new targets for therapeutic interventions.

Epilepsy is a neurological disorder characterized by an enduring predisposition to generate epileptic seizures associated to abnormal excessive or synchronous neuronal activity in the brain. Hyper-excitability of neuronal circuits may result from structural alterations (brain lesions) of various kinds, congenital or acquired. About one third of patients with epilepsy do not respond to drug treatment and in these cases, the therapeutic solution is represented by neurosurgery. This is possible only when brain lesions are limited and the removal of the epileptogenic area does not cause neurological deficits. In paediatric age, the most frequent types of brain lesions responsible for drug-resistant epilepsy are cortical dysplasia, in which a more or less circumscribed area of ​​the brain is formed abnormally. Dysplasia causes frequent seizures that have an early onset and are difficult to control due their interference with a child’s psychomotor development.

Thanks to a particular technique, the tissue removed from the brain of young patients is sectioned into slices (organotypic slices, 300 mm thick) which can be kept alive for up to 6-8 weeks by administering an artificial liquid similar to the cerebrospinal fluid, a body fluid found in the central nervous system and which has the function of protecting and nourishing the brain, and a mixture of O₂ / CO₂. The organotypic slices maintain all the characteristics of the brain including synaptic activity, neuronal circuits, electrographic characteristics of both interictal and ictal discharges, the excitation inhibition balance. Neuronal circuits consist of excitatory cells, inhibitory interneurons, and glial cells. The inhibitory interneurons, through the release of GABA, are able to synchronize the activity of hundreds of neurons with millisecond precision, giving rise to network activity that is the basis of higher cognitive functions. This preparation therefore allows to study at single neuron and network level, the cellular and molecular mechanisms underlying the pathologies affecting young patients in order to improve the diagnosis (which in this way will be more personalized) and to develop new therapeutic targets for the treatment of these disorders. Slices can be fixed for morphological identification of the recorded neurons, for immunohistochemistry and possibly for electron microscopy.

It will thus be possible to outline the origin of epileptic seizures in patients with focal cortical dysplasia with the ultimate aim of better understanding towards a personalized medicine their mechanisms in order to improve the quality of life of young patients. The joint laboratory is part of a wider collaboration between EBRI and OPBG, aimed at investigating the pathogenesis of neurodevelopmental disorders, including autism and rare genetic diseases.

 

Responsabile EBRI: Prof. Enrico Cherubini
Responsabile OPBG: Prof. Federico Vigevano