A model for functional recovery and cortical reintegration after hemifacial composite tissue allotransplantation

Abstract

Background: The ability to achieve optimal functional recovery is important in both face and hand transplantation. The purpose of this study was to develop a functional rat hemifacial transplant model optimal for studying both functional outcome and cortical reintegration in composite tissue allotransplantation.

Methods: Five syngeneic transplants with motor and sensory nerve appositions (group 1) and five syngeneic transplants without nerve appositions (group 2) were performed. Five allogeneic transplants were performed with motor and sensory nerve appositions (group 3). Lewis (RT1) rats were used for syngeneic transplants and Brown-Norway (RT1) donors and Lewis (RT1) recipients were used for allogeneic transplants. Allografts received cyclosporine A monotherapy. Functional recovery was assessed by recordings of nerve conduction velocity and cortical neural activity evoked by facial nerve and sensory (tactile) stimuli, respectively.

Results: All animals in groups 1 and 3 showed evidence of motor function return on nerve conduction testing, whereas animals in group 2, which did not have nerve appositions, did not show electrical activity on electromyographic analysis (p < 0.001). All animals in groups 1 and 3 showed evidence of reafferentation on recording from the somatosensory cortex after whisker stimulation. Animals in group 2 did not show a cortical response on stimulation of the whiskers (p < 0.001).

Conclusion: The authors have established a hemiface transplant model in the rat that has several modalities for the comprehensive study of motor and sensory recovery and cortical reintegration after composite tissue allotransplantation.

Fig. 1

Each whisker on the rat face corresponds on a 1:1 basis to a cluster of neurons called a barrel in the primary somatosensory cortex. The barrel cortex of rats, because of its clear columnar structure and direct correlation to individual whiskers on the face, has become a popular model for studying changes of cortical representational maps.

Fig. 2

A donor flap, including the entire hemiface with the mystacial pad.

Fig. 3

The underside of the hemifacial flap, showing the common carotid artery (CCA), external jugular vein (EJV), infraorbital nerve (ION), and masseter muscle. The buccal and marginal mandibular facial nerve branches are located underneath the masseter muscle.

Fig. 4

Nerve apposition of the infraorbital nerve of both donor and recipient in a syngeneic transplant.

Fig. 5

A syngeneic transplant (left) and an allogeneic (right) transplant at postoperative week 12.

Fig. 6

The nerve conduction testing of a hemifacial transplant with nerve appositions (above, experimental) shows electrical activity (asterisk), whereas nerve conduction testing of a transplant without nerve appositions (below, control) did not elicit electrical activity. The arrow indicates stimulation artifact.

Fig. 7

Deflection of the whisker upward (single arrow) in a syngeneic transplant at postoperative week 20 with nerve appositions elicited an “on” response (single asterisk), whereas return of the whisker to its normal position (double arrows) elicited an “off” response (double asterisks) of cells in the somatosensory cortex. The “on” and “off” responses indicated cortical reintegration of the flap, with return of ability of the cortex to respond to peripheral stimuli.

Fig. 8

Histologic image of the primary somatosensory cortex with cytochrome oxidase staining, Nissl counterstain, and blue filter. Histologic evaluation confirmed that the lesion (arrow) was located in the barrel cortex and thus testing was performed in the proper region of the somatosensory cortex. The asterisk indicates a barrel.