Evaluation of histocompatibility as a factor in the repair of nerve with a frozen nerve allograft

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✓ Host axons in dogs can regenerate through a long nerve allograft provided that the allograft bears only minor transplantation antigens, and is frozen and thawed before transplantation. The authors have tried to confirm this important observation in rats. Host rats received a 4-cm fresh or frozen nerve isograft (that is, a non-antigenic nerve), or a fresh or frozen nerve allograft with cells containing only minor transplantation antigens. The results showed that after 2 and 9 months only a fresh isograft permitted many host axons to traverse its entire length. Only a few host axons grew into the proximal 1 to 2 cm of a frozen isograft or into an allograft (fresh or frozen). Because frozen grafts failed, the authors examined some specimens after 2 weeks and found that freezing killed most of the Schwann cells. On the other hand, many proliferating Schwann cells were found in 2-week fresh isografts. In addition, hosts that received a frozen nerve allograft underwent regrafting after 9 months with an isograft and allograft (of the same genotype as the original nerve allograft) of nodose ganglion. These rats accepted the isograft but rejected the allograft of ganglion. It is concluded that axonal regeneration through a long frozen nerve graft fails in rats because freezing destroys Schwann cells. Moreover, a frozen nerve allograft does not induce a state of immunological tolerance, as has been suggested, because these recipients reject a second allograft. Since the present data failed to confirm findings obtained in dogs, the clinical use of a frozen nerve allograft is not recommended.

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Address reprint requests to: Andrew A. Zalewski, M.D., Building 36, Room 4D-20, National Institutes of Health, Bethesda, Maryland 20205.

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    Appearance of longitudinal sections of a normal nerve (A), and nerves grafted for 2 months (B–F). A normal nerve (A) contained many tightly packed and thickly myelinated nerve fibers (PAS stains myelin a red-purple color which in the photographs appears black). A fresh isograft (B) had many myelinated nerve fibers throughout its 4-cm length, but they were thinner and less tightly packed than normal. A fresh (C) or frozen (D) allograft lacked myelinated fibers throughout most of its distal portion; these distal segments were virtually acellular. Frozen isografts were similar to that shown in (D). Many axons were present throughout a fresh isograft (E, one axon at tip of arrow), whereas only a few axons were found in the proximal 1 to 2 cm of fresh and frozen allografts (F), or frozen isografts. A-D: PAS-hematoxylin, × 80; E, F: silver stain, × 330.

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    Appearance of longitudinal (A–C) and cross (D and E) sections of 2-week in situ degenerating host nerve (A), 2-week fresh isograft (B and D), and 2-week frozen allograft (C), and isograft (E). Schwann cells proliferated, and all but a few remnants of myelin (arrow, A) remained in an in situ degenerating nerve (A). A lesser degree of Schwann cell proliferation and more myelin debris (arrow, B) were found in a fresh isograft. The perineurial cells also survived in a fresh isograft (D, arrow points to perineurium). Massive amounts of degenerating myelin and few Schwann cells were observed in a frozen allograft (C) or frozen isograft (E). A frozen allograft but not a frozen isograft was usually surrounded (arrow, C) and infiltrated by mononuclear cells. The perineurial cells were absent from all frozen grafts (E). The arrow in E indicates where the perineurium should have been found in this frozen isograft (compare E to D). PAS-hematoxylin, × 80 (A–C) and × 330 (D, E).

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