Sensory and Motor Axonal Response to Immunosuppression Withdrawal in Long Peripheral Nerve Allografts

Rajiv Midha, MD, MSc
Slnudeslma Nag
Catherine A. Munro, MSc
Lee C. Ang,MD (Toronto, ON Canada)

Immunological rejection of allografts in peripheral nerve repair remains a problem. Previous work indicated that the nature of the end–organ fails to influence axonal degeneration across short nerve allografts. The present study examines the effect of proximal fibre type on degeneration in long allografts after immunosuppression withdrawal. We hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. Also, we predicted that graft length influences axon survival.

ACI rat nerve segments (4cm long) were grafted into peroneal, sural or saphenous nerve gaps (n=121) in Lewis rats. In a subset of rats, the left dorsal root ganglia of L4–6 were ablated 6 weeks prior to grafting, creating "pure motor" nerves. Rats received 12 weeks of Cyclosporin A (CsA) immunosuppressive after surgery. At sacrifice (12–18 weeks postsurgery), electrophysiologic studies were performed and tissue collected for histomorphometry. Total fibre counts for mid–graft samples (expressed as % of 12 week baseline) at 16 weeks were as follows: saphenous 78%, ablated sural 59%, ablated peroneal, 41%, non–ablated sural 0%, non–ablated peroneal 1%. By 18 week, total fibre counts were: saphenous 32%, ablated sural 6%, ablated peroneal, 8%, non–ablated sural 2%, non–ablated peroneal 18%. Total fibre count data demonstrate a dramatic dropout of fibres in long nerve allografts following CsA withdrawal. However, the extent and temporal pattern of degeneration varied between nerve types. Sensory fibres were most resistant to rejection. The relative resilience of "pure motor" nerves compared with mixed nerves indicated a mild protective effect.