Effects Of Postoperative Irradiation On Rabbit Orthotopic Transplanted Sciatic Nerve Regeneration: An Experimental Study

AIM: To investigate the effect of postoperative radiotherapy onrabbit sciatic nerve autograft regeneration.METHODS: 70 adult New Zealand white rabbits underwent 2cmright sciatic nerve autografting. Then, they were randomly divided into toexperimental control group (N=14) and experimental group. The rabbitsfrom the experimental group received a total dose of 28Gy or 36Gyfractional irradiation at the lesion site 2 or 4 weeks after surgery. So theexperimental group was further divided into four subgroups: 2w-28Gygroup, 2w-36Gy group, 4w-28Gy group and 4w-36Gy group (n=14). Therabbits from experimental control group received no further treatment,and the left sciatic nerve served as normal control. After survived for 2 or4 months, general observation, electrophysiologic study, pathologic andimmunohistochemical staining, and transmission electron microscope(TEM) were used to evaluate structure of the distal transplanted nervesegment.RESULTS: 1. General observation: all rabbits after sciatic nerveautografting appeared hind limb dropping, abolition of the claw extendingreflex and some developed ulcer formation; 2 months later, the walkingand claw extending reflex of rabbits from both experimental controlgroup and experimental groups were recovered much, but still worse thannormal, and the ulcer healing was better in experimental control groupthan experimental groups. 4 months later, the walking and claw extendingreflex of all rabbits recovered roughly to the normal level, and the ulcerhealing from all groups was almost complete.2. Electrophysiologic study: 2 months after sciatic nerveautografting, the nerve conduction velocity (CV) and action potential(AMP) decreased comparing with normal control (P＜0.05), 4 monthslater, CV and AMP recoverd almost to normal level (P＞0.05). 2 monthsafter orthotopic transplantation, the CV and AMP of all experimentalgroups were significantly decreased comparing with normal control(P＞0.05), with those in 2w-36Gy group at the lowest level; the CV and AMP of 2w-28Gy group, 2w-36Gy group and 4w-36Gy group were alsolowed than those in experimental control group (P＜0.05). At thepostoperation time 4 months, the CV and AMP of all experimental groupswere recoverd at some extent; those in 4w-28Gy group were almostreturned to normal level (P＞0.05), but those from 2w-36Gy group werestill lower than normal control and experimental group (P＜0.05).3. Pathologic staining showed that there were severe axonaldegeneration and vacuolar degeneration of myelin sheath in experimentalcontrol group 2 month after operation; 4 months later, the structure of thenerve graft recovered to normal, though there were still some vacuolardegeneration of myelin sheath. There were more severe axonaldegeneration and vacuolar degeneration of myelin sheath, and lessSchwann cells and vascular proliferation in experimental groups thanexperimental control group 2 months after operation, while 2w-36Gygroup was the worst one. 4 months later, the graft recovered much, butthere were still some vacuolar degeneration of myelin sheath.4. NF immunochemistry staining denoted that 2 months after, NFimmunoreactivity was significantly weaker in experimental control groupand experimental groups than in normal one, and experimental groupswere significantly weaker than experimental control; The differencesbetween the different dose groups(28Gy vs 36Gy) or different beginningtime groups(2-week vs 4-week) were also significant(P＜0.05); 4 monthslater, that of experimental control and 4w-28Gy groups were equal tonormal control (P＞0.05), that of 2w-36Gy group was still significantlyweaker than normal and control groups.5. TEM showed that in experimental control group, there weredegeneration and tissue necrosis 2 months later, but some newly thinregenerated neuronal fibers and blood capillaries could be seen; after 4months, there were abundant newly regenerated neuronal fibers withthick myelin sheath and blood capillaries. In experimental groups, therewere more severe neuronal degeneration, and tissue necrosis than that inexperimental control group, and less newly regenerated neuronal fibersand blood capillaries, especially in 2w-36Gy group, in which there wereno axons, but severe hemorrhage and necrosis. 4 months later, the structures of nerve graft in experimental groups recovered greatly,especially in 4w-28Gy group, in which there were abundant regeneratednerve fibers with thick myelin sheath and blood vessels, though therewere some curled and emboled myelin sheath. In 2w-36Gy group, therewere some regenerated nerve fibers with thin curled and emboled meylinsheath and blood vessels.CONCLUSION: 1. Fractionated postoperation radiotherapysignificantly affected the morphology and function of orthotopictransplanted peripheral nerve; and as the survive time prolonged, 4 monthafter operation, the morphology and function of the orthotopictransplanted peripheral nerve almost returned to normal level. 2. Theinhibitive influences of postoperative irradiation on regeneration oforthotopic transplanted peripheral nerve had close relationship withirradiation dose, the treatment dose (36Gy) affected more, and preventivedose (28Gy) had less influence. 3. The inhibitive influences ofpostoperative irradiation on orthotopic transplanted peripheral nerveregeneration also depended on irradiation beginning time, givingirradiation 2 weeks after operation affected more, and 4 weeks had lessinfluence.