Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus

Abstract

The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor

“…In the past decades, the implementation of clinical standards on synchrotron x-ray treatment stations has progressed, in terms of medical physics and radiation delivery safety, and now allow a safe clinical transfer of the technique. A first large animal MRT study in healthy minipigs has shown that the radio-ablation of the right caudate nucleus could be safely and effectively performed (12). This first veterinary patient case-report on a dog with a spontaneous brain tumor confirms the radiotolerance of normal tissues during the (sub)acute phase after microbeam exposures.…”

“…The continuous perfusion of normal tissues is maintained (6). A recent study has shown that multidirectional MRT exposures of intracranial tumors in rats leads to 2.5-fold higher tumor control probability compared with conventional radiation protocols (7) ; the low normal tissue complication probability of such MRT strategies has not only been revealed in normal brain tissues in rodents (7), but also in minipigs (12) and developing brain of piglets (13).…”

A high‐resolution dose calculation engine for X‐ray microbeams radiation therapy

“…PenMRT enables planning and optimization of MRT treatments using high‐resolution dose metrics when several microbeams arrays are used. Based on a recent hypothesis in MRT, the radiotherapy toxicity and the treatment efficiency is linked to valley and peak doses, respectively 8,61 . However, the role of the array of microbeams, the hot spots and their spatial distribution in multidirectional irradiation is still unknown.…”

“…This is of particular interest for treatment planning in MRT, with dose metrics representing the complexity of the irradiation. So far, the treatment plans in MRT 8,61 trials are performed using the hybrid algorithm, 37 which has a limited spatial resolution due to macroscopic rendering of separated peak and valley dose maps. 17 PenMRT enables planning and optimization of MRT treatments using high-resolution dose metrics when several microbeams arrays are used.…”

“…Based on a recent hypothesis in MRT, the radiotherapy toxicity and the treatment efficiency is linked to valley and peak doses, respectively. 8,61 However, the role of the array of microbeams, the hot spots and their spatial distribution in multidirectional irradiation is still unknown. A recent study by Cahoon et al 62 is pointing to the potential role of the bystander effects linked to the over irradiated cells in the beam passage.…”