Revascularization of Peripheral Nerve Autografts and Allografts

Abstract

We investigated the ability of anti-ICAM-1 monoclonal antibodies to reduce endothelial cell damage by assessing microvascular permeability and microcirculatory function during the acute phase of allograft rejection. The composite rat hindlimb-cremaster muscle transplantation model was employed in three experimental groups of 18 animals each. Isograft control transplantations were performed between genetically identical Lewis (LEW, RT11) rats. Allograft transplantations were performed across a major histocompatibility barrier between Lewis-Brown-Norway (LBN, RT-11+n), and Lewis (LEW, RT11) rats. In addition, a third group of animals receiving allografts was treated with 1 mg/kg/day of anti-ICAM-1 monoclonal antibody. After 24 hours, 72 hours, and 7 days, we measured microvascular permeability, leukocyte activation, functional capillary perfusion, red blood cell velocity, vessel diameters, and endothelial edema index in six animals per each follow-up period. Endothelial cell damage was assessed by measuring graft permeability to fluorescein isothiocyanate-labeled albumin (0.2 ml/100 g body weight) with computer-aided image analysis. Mean microvascular permeability was lower in the treated allograft group than in untreated controls at all follow-up times (p<0.001). In addition, anti-ICAM-1 treatment significantly reduced the activation of sticking leukocytes at 24 and 72 hours (p<0.001) and the activation of transmigrating leukocytes at 72 hours and 7 days (p<0.05). The allografts presented a characteristic microcirculatory pattern of acute rejection as early as 24 hours after transplantation. The dysfunction of the endothelial cell barrier at all time points was indicated by significant increases in the degree of allograft macromolecular permeability and in the number of activated sticking and transmigrating leukocytes. Treatment with anti-ICAM-1 antibodies significantly reduced the surge of leukocytes in the allograft transplants and protected the endothelial barrier from the acute effects of transplantation trauma.

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

“…Reperfusion appeared to occur in an all-or-none pattern consistent with the mechanism of donor vascular network reconnection to recipient vessels. Though this has not been previously studied in orthotopic tracheal grafts, other studies have demonstrated similar mechanics of revascularization as well as time course in avascular grafts such as skin autografts (19,20) and peripheral nerve allografts (21). Interestingly, the transgenic Tie2/β-galactosidase recipients had many cells in the allograft expressing β-galactosidase.…”

Peripheral nerve and neuromuscular allotransplantation: Current status

“…Regeneration into nerve grafts is similar; however, the graft must be revascularized early to ensure Schwann cell survival, and minimize fibrous tissue replacement. 2,3 Once the axons have traversed the graft they can be supported by the distal nerve segment and ultimately their end organ (i.e., skin, sensory receptor, neuromuscular junction, or muscle spindle). The axons that reach inappropriate targets or no targets are pruned.…”

“…Recipients of stored allografts require lower dosages of CsA immunosuppression compared to fresh allografts. 21 The use of a vascularized allograft offers theoretical advantages: (1) to allow en bloc reconstruction of nerve plexi; (2) to enhance the rate of nerve regeneration and (3) to permit the utilization of larger "trunk" grafts without the problem of central necrosis. 22,23 When this methodology is applied to the nerve allograft, several interesting observations have been made.…”

A Preliminary Assessment of the Utility of Large-Caliber Processed Nerve Allografts for the Repair of Upper Extremity Nerve Injuries

“…1 Virginia Commonwealth University, Richmond, VA, USA 2 The Buncke Clinic, San Francisco, CA, USA PNA comes in a 2-to 3-mm diameter option, which can be stacked into cables in an analogous fashion to autograft for bridging gaps in large-diameter nerves. However, PNA is also available in diameters up to 4 to 5 mm that can be used as a single graft to bridge a gap in large-diameter nerves, thus eliminating the need for multicable strands.…”