Several studies were performed to evaluate factors which might lead to the use of foreign grafts to aid in the repair of injured nervous tissue. A comparative study was performed to determine whether the immunosuppressive agent Cyclosporin-A (Cy-A) prevented the rejection of xenogeneic (cross-species) neurons. The results demonstrated that mouse and hamster but not guinea pig neurons survived in grafts in Cy-A treated rats. However, no neurons survived in any other donor-host combination of those species (e.g., rat to hamster). The effect of Cy-A on xenografts is therefore unpredictable, and clinical implications drawn from data generated in a single donor-host combination must be guarded. In another study, we tried to determine the prime target tissue of the immune response directed towards a nerve allograft. We found that the vasucular sysem was rejected first leading to infarction of the graft and the disappearance of Schwann cells from it. Another experiment was done to evaluate the status of the blood-nerve barrier in surviving nerve allografts in Cy-A immunosuppressed rats. The endoneurial graft vessels became permeable to intravenously injected horseradish peroxidase (HRP) during the acute phase of Wallerian degeneration, but they restored their normal impermeability following the remyelination of host axons that had regenerated through the graft. The perineurial-nerve barrier in allografts, as in normal nerve, remained impermeable to HRP that leaked from epineurial vessels throughout the period of graft survival. Other data revealed that in rats a nerve graft could be cryopreserved (i.e., frozen and the cells in it remain alive) in dimethyl sulfoxide and later used to repair injured nerve. This result indicates the feasibility of establishing banks of cryopreserved nerves since they function, as conduits for host axonal growth, better than frozen, killed grafts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002254-10
Application #
3968945
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code