Abstract
Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.
Highlights
Microscopic arrays of X-ray beams originating from a synchrotron source can induce the equivalent of a microsurgical neocortical or hippocampal incision by delivering very high doses of radiation to tissue slices of microscopic thickness
The dose profile into the target consists of high doses along the microbeam path and low doses in the spaces between them (Fig. 1A)
Focal irradiation of an epileptic focus through SRS is an emerging treatment for medically refractory seizures, providing a non-surgical approach which is mainly limited by the delay of efficacy and side-effects
Summary
Microscopic arrays of X-ray beams originating from a synchrotron source can induce the equivalent of a microsurgical neocortical or hippocampal incision by delivering very high doses of radiation to tissue slices of microscopic thickness. Synchrotron-generated cortical transections provide a microradiosurgical equivalent of multiple subpial transections (MST), a non resective surgical technique developed to treat patients with medically-refractory epilepsy involving eloquent cortex[2,3,4] This technique requires the placement of vertical incisions through the epileptic cortex in order to cut the horizontal axons responsible of the propagation of seizures while preserving the vertical axons subserving neurological functions. Microbeam transections have been performed over an epileptogenic focus located in sensorimotor cortex, with almost immediate abolition of seizures and excellent preservation of motor function[5] These results suggested further investigations to assess the potential of microbeam transections to modulate cortical and hippocampal functions and to treat focal epilepsy and other brain disorders as well as brain tumors. We tested the hypothesis that microbeams irradiation of the hippocampus is safe and does not induce severe side effects in healthy rats
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