Tissue-engineered Conduit Promote Sciatic Nerve Regeneration Following Radiation-induced Injury:Monitored With Magnetic Resonance Imaging

Objective:To observe the longitudinal changes of peripheral nerve repair with chitosan nerve conduits in rat model of radiation-induced neuropathy. To determine whether the nerve injury and repair process could be monitored by magnetic resonance imaging (MRI) and electromyogram (EMG).Materials and methods:The animal care procedures and study protocol was approved by the institutional Animal Use and Care Committee of Kunming Medical University.55 adult Sprague-Dawley rats were used to establish the sciatic nerve radiation injury model. Four months after the right lower limbs exposed to 40 Gy of radiation, the 42 rats remained were divided randomly into three groups. The chitosan conduit were implanted into the radiation injured sciatic nerves with (group A, n=14) or without (group B, n=14) mesenchymal stem cells (MSCs).14 rats were left untreated as a control (group C). Following the treatment, the sciatic nerve imaging and a complete neurological exam, including low limb function evaluation and nerve conduction studies, were performed monthly for another 8 months. Magnetic resonance neurography (MRN) including two-dimensional fast spin echo (2D FSE) T2-weighted sequence and Gd-DTPA enhanced T1 weighted imaging. The standard signal intensity (SI) and finally histological assessments were compared among the experimental and control groups. The statistic analysis including repeated-measures analysis of variance and multiple pairwise comparisons were used.Results:Four months after the injury, the foot drop and limp were appeared in most rats, and the compound muscle action potentials (CMAPs) and sciatic function index (SFI) were declined in the injured right limbs. This time point had been chosen for the tissue-constructed tube implantation. Two months after the operation, the CMAPs and SFI were kept declining in all groups without difference (Z=1.316; p=0.297). In the following months, the sciatic nerves in Group A and B (which underwent nerve conduit implantation) displayed more progressive function recovery than the control Group C, but no difference was found whether or not the MSCs had been used. To the end of 12 months after the radiation injury (8 months after the conduits implantation), the histology results indicated Group A had better remyelination than other two groups (Z= 2.077; p= 0.038), compared with difference in latency values and SFI score among all three groups (Z= 1.245; p= 0.032).About 3 months after the radiation injury, focal nerve enlargement and hyperintensity had been observed in MR T2WI imaging. Meanwhile the perineurium and connecting muscle enhancement had also been manifested by T1WI imaging. These changes were lasting for nearly 8 months, and the measured SI among groups were significant different (P<0.05) in most of time. The SI in group A was declined more rapidly than others after the chitosan tube implantation.Conclusion:Tissue constructed nerve conduits can be used to repair radiation injured peripheral nerves in rat model. The T2WI and enhanced T1WI magnetic resonance imaging were useful in monitoring nerve repair process, which was non invasive and visualized comparing with biopsy and electrophysiological examination.