Radiation-induced changes in peripheral nerve by stereotactic radiosurgery: a study on the sciatic nerve of rabbit

A large fractional dose in radiotherapy produces better radiobiological results, but there is always a concern of radiation-induced damage to the normal tissues, especially peripheral nerves. This study was to evaluate the radiation-induced changes of sciatic nerve treated by stereotactic radiosurgery (SRS) in rabbit. A localization test was performed on 3 rabbits to determine the reference landmarks to the location of the sciatic nerve of rabbit in CT. Another 12 rabbits were irradiated by a dose of 25 Gy at the sciatic nerve using SRS with 5 non-coplanar arcs. The rabbits were randomized into 3 groups and euthanised at 3, 5, and 7 months after radiotherapy, respectively. Apart from the sensory and motor tests performed on the rabbits, segments of the sciatic nerve were prepared for hematoxylin and eosin staining. Histologic and ultra-structural examinations including morphometric analyses were conducted and compared with the control (non-irradiated side). Apart from the loosening of myelin layers at 5 months, no prominent changes were shown at 3 and 5 months after irradiation. At 7 months, despite the fact that the sensation and motor function tests remained intact, ultra-structural examination showed obvious vacuolation, degeneration and necrosis of the axons with myelin fragmentation. In addition, morphometric analysis indicated that, when compared with the control, there was significant reduction in fiber diameter, increase of myelin thickness and decrease of G ratio (P < 0.01). Although it remained functionally intact, a focal single dose of 25 Gy caused significant microscopic damage to the rabbit sciatic nerve at 7 months after irradiation. Escalating doses with large single fractional dose involving peripheral nerves should be carried out with caution.