Abstract

Microbeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats underwent irradiation with arrays of parallel microbeams. Beam thickness, spacing and incident dose were 100 or 600 µm, 400 or 1200 µm and 360 or 150 Gy, respectively. Motor performance was carried over a 3-month period. Three months after irradiation rats were sacrificed to evaluate the effects of irradiation on brain tissues by histology and immunohistochemistry. Microbeam irradiation of sensorimotor cortex did not affect weight gain and motor performance. No gross signs of paralysis or paresis were also observed. The cortical architecture was not altered, despite the presence of cell death along the irradiation path. Reactive gliosis was evident in the microbeam path of rats irradiated with 150 Gy, whereas no increase was observed in rats irradiated with 360 Gy.

Highlights

  • Microbeam radiation therapy (MRT) is a developing technique using X-ray microplanar beams generated by a synchrotron radiation X-ray source, with potential translation to humans

  • The pathophysiological bases of this treatment is the use of microbeams to produce cerebral cortex transections in order to segregate cortical columns by sawing their horizontal connections, to what is produced by the surgical non-resective technique named multiple subpial transections (MSTs)

  • Irradiation of the sensorimotor cortex did not induce any gross sign of paralysis or paresis over a 3-month period

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Summary

Introduction

Microbeam radiation therapy (MRT) is a developing technique using X-ray microplanar beams ( known as microbeams) generated by a synchrotron radiation X-ray source, with potential translation to humans. MSTs are employed to treat selected cases of focal medically refractory epilepsy involving eloquent cortices[15,16] Such microbeam transections provide a highly innovative and non-invasive way to generate cortical microscopic cuts of specific size and spacing, offering a novel attractive tool to study cortical function and to develop new approaches for the treatment of drug-resistant focal epilepsy. Growing evidence show the remarkable tolerance of the brain to thin microbeams (25 to 100 μm) delivering doses up to 1000 Gy. thick beams, called minibeams[17,18] are much more likely to find clinical application because they could be more produced by sources different from synchrotrons[19], markedly facilitating the technique application by medium-size hospitals. Of brain cortex to parallel transections induced with thin (100 μm) or thick (600 μm) beams, delivering 360 or 150 Gy, respectively, in healthy rats

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