Midha R, Munro C A, Mackinnon S E, Ang L C
Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, ON, Canada.
J Neuropathol Exp Neurol. 1997 Apr;56(4):421-34. doi: 10.1097/00005072-199704000-00011.
Previous studies have shown both survival and loss of regenerated host axons within nerve allograft segments after withdrawal of Cyclosporin A (CsA) immunosuppression. We hypothesized that the nature of end-organ reinnervation may influence the response of the axon, with survival of axons for appropriate innervation vs degeneration for inappropriate innervation. The rat femoral nerve model was chosen, as it has approximately equal sensory (S) and motor (M) divisions. Four ACI rat peroneal nerve allografts were sutured in straight (right leg: MM and SS) or switched (left leg; MS and SM) orientation in each femoral nerve transection gap in each Lewis rat recipient. Rats received CsA for 8 weeks to allow end-organ reinnervation, after which immunosuppression was discontinued. Rats were killed at various times thereafter, and underwent histologic and morphometric analysis of the graft segment axons. The regenerated axon population in the allograft reflected the nerve of origin: significantly more but smaller fibers when the proximal nerve was sensory and fewer but larger fibers when the proximal nerve was motor. After CsA withdrawal, there was a marked decrease of host axons as part of an ensuing rejection episode. The overall proportional decrease of axons was similar across all nerve orientation groups and, therefore, did not appear to be influenced by the nerve of origin or by the end-organ. However, the sensory proximal groups (SS and SM) contained more mature, noninjured fibers, while the motor proximal groups (MM and MS) contained significantly more degeneration and newly regenerating axons. We conclude that the motor or sensory nerve origin of the host axon, rather than the end-organ, influences axon survival after immunosuppression cessation. It is hypothesized that sensory axons may be more resilient while motor axons are selectively vulnerable to this second injury.
先前的研究表明，停用环孢素A（CsA）免疫抑制后，同种异体神经移植段内再生的宿主轴突既有存活的，也有丧失的。我们推测，终末器官再支配的性质可能会影响轴突的反应，轴突会因适当的再支配而存活，因不适当的再支配而退化。选择大鼠股神经模型，因为它的感觉（S）和运动（M）分支大致相等。在每只Lewis大鼠受体的每个股神经横断间隙中，将四根ACI大鼠腓总神经同种异体移植以直线（右腿：MM和SS）或交叉（左腿：MS和SM）方向缝合。大鼠接受CsA治疗8周，以实现终末器官再支配，之后停止免疫抑制。此后在不同时间处死大鼠，并对移植段轴突进行组织学和形态计量学分析。同种异体移植中的再生轴突群体反映了其起源神经：当近端神经为感觉神经时，纤维数量明显更多但更细；当近端神经为运动神经时，纤维数量更少但更粗。停用CsA后，作为随后排斥反应的一部分，宿主轴突显著减少。轴突的总体比例下降在所有神经方向组中相似，因此似乎不受起源神经或终末器官的影响。然而，感觉近端组（SS和SM）包含更多成熟、未受损的纤维，而运动近端组（MM和MS）包含明显更多的退化和新再生轴突。我们得出结论，宿主轴突的运动或感觉神经起源而非终末器官，会影响免疫抑制停止后轴突的存活。据推测，感觉轴突可能更具弹性，而运动轴突则对这种二次损伤选择性敏感。
