Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy.

Benoît Pouyatos 1, * Raphaël Serduc 2 Mathilde Chipaux 3, 4 Tanguy Chabrol 5 Elke Bräuer-Krisch 6 Christian Nemoz 6 Hervé Mathieu 7 Olivier David 1 Luc Renaud 8 Yolanda Prezado 6 Jean Albert Laissue 9 François Estève 2 Stéphane Charpier 3 Antoine Depaulis 10
* Auteur correspondant
1 INSERM U836, équipe 11, Fonctions cérébrales et neuromodulation
GIN - Grenoble Institut des Neurosciences
2 INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale
GIN - Grenoble Institut des Neurosciences
3 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
4 Service de neurochirurgie pédiatrique
5 INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques
GIN - Grenoble Institut des Neurosciences
6 ID17 - Biomedical Beamline
7 GIN - Grenoble Institut des Neurosciences
8 CERCO - Centre de recherche cerveau et cognition
9 Oncology - Pathology - Anatomy
10 INSERM U836, équipe 9, Dynamique des réseaux synchrones épileptiques
GIN - Grenoble Institut des Neurosciences, Service de neurochirurgie pédiatrique
Abstract : Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.
Keywords : Epilepsy Animal model Spike-Wave discharges Radiotherapy Synchrotron x-ray microbeams intracellular recordings in vivo
Type de document :
Article dans une revue
Neurobiology of Disease, Elsevier, 2013, 51, pp.152-60. 〈10.1016/j.nbd.2012.11.005〉
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Benoît Pouyatos, Raphaël Serduc, Mathilde Chipaux, Tanguy Chabrol, Elke Bräuer-Krisch, et al.. Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy.. Neurobiology of Disease, Elsevier, 2013, 51, pp.152-60. 〈10.1016/j.nbd.2012.11.005〉. 〈inserm-00794543〉

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