Extended survival and function of peripheral nerve allografts after cessation of long-term cyclosporin administration in rats

Frazier, Joel L.; Yu, Leonard T.; Rhee, Edward K.; Shaw, Leslie M.; LaRossa, Don; Rostami, Abdolmohammad

doi:10.1016/0363-5023(93)90252-x

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…In 1993, Frazieretcil. 28 in a similar model, noted no electrophysiologic signs of rejection in any of 22 allograft recipients immunosuppressed for 8 months; however, rejection occurred in five of 22 (23 percent) allograft recipients immunosuppressed for "only" 5 months. For up to 58 weeks after cessation of CsA, there were no significant changes in conduction velocity in the "surviving" 5-month and the 8-month groups.…”

Section: Resultsmentioning

confidence: 84%

“…29 " 31 demonstrate that PNAs will be rejected following cessation of CsA immunosuppression (loss of axons, cellular elements, and graft function); however, the weaknesses of their study include inadequate duration of CsA therapy; small sample size; short survival times after CsA withdrawal; and proximal but not distal nerve repair. Yu et al 25 and Frazier et al 28 demonstrate rejection with complete loss of function after cessation of temporary immunosuppression in 57 percent (4 of 7) and 23 percent (5 of 22) of allograft recipients, respectively, in a tibial rather than a sciatic nerve injury model involving Brown Norway recipients and Lewis donors.…”

Section: Resultsmentioning

confidence: 98%

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Peripheral-Nerve Allotransplantation in Rats Immunosuppressed with Transient or Long-Term FK-506

Weinzweig¹,

Grindel²,

Gonzalez³

et al. 1996

J reconstr Microsurg

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The purpose of this study was to assess regeneration across peripheral-nerve allografts by electro-physiologic methods, in rats receiving transient or long-term immunosuppression with FK-506. Lewis rats (LEW, RT1(1)) were recipients of sciatic nerve isografts or allografts from donor LEW or ACI (RT1a) rats, respectively. This latter donor-recipient inbred combination represents a major histoincompatible mismatch. The sciatic nerve was exposed through a gluteal muscle-splitting incision. A 2.0-cm segment of nerve was excised and a 2.5-cm graft sutured into the gap in epineural fashion. Seven groups (n = 8 each) included: Group 1--isograft control (LEW/LEW): Group 2--allograft control (LEW/ACI); Group 3--allografts receiving cyclosporin A (CsA) (10 mg/kg BW/day) subcutaneously for 2 weeks; Group 4--CsA for 2 weeks then biweekly subcutaneously; Group 5--FK-506 (10 mg/kg BW) intramuscularly by single injection; Group 6--FK-506 (1.0 mg/kg BW/day) for 2 weeks then biweekly intramuscularly; and Group 7--FK-506 for 2 weeks then biweekly intramuscularly. At 7 months, conduction velocities were determined and statistical analysis was performed. Excellent neural regeneration was observed in the isograft group (61.6 m/s), the allograft groups receiving long-term immunosuppression with either CsA (62.3 m/s) or FK-506 (61.7 m/s), and the transient FK-506 group (60.2 m/s). The transient CsA group (41.9 m/s), the allograft control group (53.4 m/s), and the single-dose FK-506 group (40.8 m/s) demonstrated significantly poorer results. Transient immunosuppression with FK-506 allowed for the restoration of anatomic and physiologic function of a peripheral-nerve allograft in inbred rats.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 98%

Peripheral-Nerve Allotransplantation in Rats Immunosuppressed with Transient or Long-Term FK-506

Weinzweig¹,

Grindel²,

Gonzalez³

et al. 1996

J reconstr Microsurg

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“…The efficacy of temporary host immunosuppression has been suggested by several authors. [4][5][6][7]9,10 Common to these studies is the observation of nerve allograft and donor-derived Schwann-cell rejection, with demyelination and axonal loss after withdrawal of immunosuppression. Several authors [11][12][13][19][20][21] have reported that donorderived Schwann cells are rejected in the allograft, and that host-derived Schwann cells migrate into the graft together with axonal sprouting.…”

Section: Discussionmentioning

confidence: 99%

“…Since a minimal positive area of MN4-91-6 antibody was found after the rejection response subsided, we considered the possibility that partial immunologic tolerance had been induced in the donor-derived Schwann cells. Some authors 7,27 have reported that immunologic tolerance can be induced in nerve allografts after withdrawal of cyclosporin. However, further study is needed to confirm whether or not immunologic tolerance is induced.…”

Section: Discussionmentioning

confidence: 99%

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Interposed Autologous Nerve Segment Stimulates Nerve Regeneration in Peripheral Nerve Allografts in a Rat Model

Sugita

Ishida²,

Ikuta³

et al. 2004

J reconstr Microsurg

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The ability of autologous nerve segments interposed between allografts, to increase the total nerve-gap distance, was studied. Sciatic nerve allografts were carried out in a rat model. A 15-mm nerve gap was repaired with a 25-mm nerve graft (interposed group: allo-auto-allograft; control group: allo-allo-allograft). Cyclosporin was given for 12 weeks. Nerve regeneration was evaluated using the weight of the anterior tibial muscle and histologic, morphometric and immunohistochemical analyses at 12, 13, 14, 15, 16, 20, and 24 weeks. Nerve regeneration in the interposed group was statistically significantly better than that in the control group. The authors concluded that a nerve allograft with interposed autograft may enhance nerve regeneration in this model, because of the migration of host-derived Schwann cells into the graft from not only the proximal and distal host nerve stumps, but also the interposed autograft.

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Nerve regenerating effect of short‐course administration of cyclosporine after fresh peripheral nerve allotransplantation in the rat: Comparison of nerve regeneration using different forms of donor nerve allografts

1995

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There is almost universal agreement that if cyclosporine (CsA), which is a potent immunosuppressant, is temporarily administered after surgery, regenerated axons will be maintained even after withdrawal of CsA following peripheral nerve allotransplantation. Thus, this experimental study was conducted to investigate whether a difference in donor nerve form, including thickness and length, influences nerve regeneration after withdrawal of immunosuppression with CsA. The findings suggest that as a result of immunosuppression with CsA, large-diameter nerve grafts are better able to induce nerve regeneration than small-diameter grafts, and after withdrawal of the immunosuppressant, thick nerve grafts are also better able to preserve regenerated axons against the rejection reaction than thin grafts. With regard to the length of the grafted nerve, short nerve allografts yield higher axon counts than long ones, the same as with autografts. The best way to induce nerve regeneration appears to be to transplant a short, thick nerve allograft, which is definitely capable of inducing many regenerated axons.

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Extended survival and function of peripheral nerve allografts after cessation of long-term cyclosporin administration in rats

Cited by 10 publications

References 12 publications

Peripheral-Nerve Allotransplantation in Rats Immunosuppressed with Transient or Long-Term FK-506

Peripheral-Nerve Allotransplantation in Rats Immunosuppressed with Transient or Long-Term FK-506

Interposed Autologous Nerve Segment Stimulates Nerve Regeneration in Peripheral Nerve Allografts in a Rat Model

Nerve regenerating effect of short‐course administration of cyclosporine after fresh peripheral nerve allotransplantation in the rat: Comparison of nerve regeneration using different forms of donor nerve allografts

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