title: Nerve regeneration in rat limb allografts: evaluation of acute rejection rescue.
abstract: BACKGROUND
  Successful nerve regeneration is critical to the functional success of composite tissue allografts. The present study was designed to characterize the effect of acute rejection on nerve regeneration and functional recovery in the setting of orthotopic limb transplantation.
  
  
  METHODS
  A rat orthotopic limb transplantation model was used to evaluate the effects of acute rejection on nerve regeneration and motor recovery. Continuous administration of FK506 (full suppression), administration of FK506 for the first 8 of 12 weeks (late rejection), or delayed administration of FK506/dexamethasone following noticeable rejection (early rejection) was used to preclude or induce rejection following limb transplantation. Twelve weeks postoperatively, nerve regeneration was assessed by means of histomorphometric analysis of explanted sciatic nerve, and motor recovery was assessed by means of evoked muscle force measurement in extensor digitorum longus muscle.
  
  
  RESULTS
  A single episode of acute rejection that occurs immediately or late after reconstruction does not significantly alter the number of regenerating axonal fibers. Acute rejection occurring late after reconstruction adversely affects extensor digitorum longus muscle function in composite tissue allografts.
  
  
  CONCLUSIONS
  Collected data reinforce that adequate immunosuppressant administration in cases of allogeneic limb transplantation ensures levels of nerve regeneration and motor functional recovery equivalent to that of syngeneic transplants. Prompt rescue following acute rejection was further demonstrated not to significantly affect nerve regeneration and functional recovery postoperatively. However, instances of acute rejection that occur late after reconstruction affect graft function. In total, the present study begins to characterize the effect of immunosuppression regimens on nerve regeneration and motor recovery in the setting of composite tissue allografts.
authors.affiliation: St. Louis, Mo. From the Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, and the Department of Biomedical Engineering, Washington University in St. Louis.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Matthew R
authors.initials: MR
authors.lastname: MacEwan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hunter
authors.forename: Scott
authors.initials: S
authors.lastname: Farber
authors.forename: Piyaraj
authors.initials: P
authors.lastname: Newton
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tung
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mackinnon
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D000208:Acute Disease; D000818:Animals; D005121:Extremities / Q000294:innervation* / Q000637:transplantation*; D006084:Graft Rejection / Q000188:drug therapy; D008297:Male; D009416:Nerve Regeneration; D051381:Rats; D011917:Rats, Inbred Lew
references.citation: J Neuropathol Exp Neurol. 1994 May;53(3):316-22
references.pmid: 8176414
references.citation: Ann Plast Surg. 2005 Apr;54(4):420-7
references.pmid: 15785285
references.citation: Plast Reconstr Surg. 2000 Apr;105(5):1704-11
references.pmid: 10809101
references.citation: Ann Plast Surg. 1984 Mar;12(3):249-55
references.pmid: 6609665
references.citation: Exp Neurol. 2010 Oct;225(2):310-9
references.pmid: 20633557
references.citation: J Hand Surg Am. 1995 Jan;20(1):77-87
references.pmid: 7536766
references.citation: Microsurgery. 2001;21(7):298-305
references.pmid: 11754429
references.citation: J Hand Surg Am. 2011 Nov;36(11):1862-7
references.pmid: 22036285
references.citation: Muscle Nerve. 2000 Apr;23(4):633-40
references.pmid: 10716776
references.citation: Plast Reconstr Surg. 2003 Oct;112(5):1336-46
references.pmid: 14504517
references.citation: Plast Reconstr Surg. 2001 May;107(6):1419-29
references.pmid: 11335811
references.citation: Lancet. 1999 Apr 17;353(9161):1315-20
references.pmid: 10218530
references.citation: Prog Neurobiol. 1999 Jun;58(3):233-47
references.pmid: 10341362
references.citation: Neurorehabil Neural Repair. 2012 Jul-Aug;26(6):570-80
references.pmid: 22291040
references.citation: J Neuropathol Exp Neurol. 2005 Jul;64(7):613-22
references.pmid: 16042313
references.citation: Am J Transplant. 2010 Feb;10(2):251-61
references.pmid: 20041866
references.citation: Exp Neurol. 2002 May;175(1):127-37
references.pmid: 12009765
references.citation: Ann N Y Acad Sci. 1993 Nov 30;696:20-30
references.pmid: 7509131
references.citation: Microsurgery. 2001;21(4):153-5
references.pmid: 11494383
references.citation: Ann N Y Acad Sci. 1979;317:512-31
references.pmid: 289329
references.citation: J Reconstr Microsurg. 2001 May;17(4):267-73
references.pmid: 11396589
references.citation: J Neurosci Methods. 2007 Oct 15;166(1):116-24
references.pmid: 17675163
references.citation: Muscle Nerve. 2002 Jan;25(1):31-8
references.pmid: 11754182
references.citation: Restor Neurol Neurosci. 1994 Jan 1;7(1):45-57
references.pmid: 21551771
references.citation: Ann Plast Surg. 2002 Dec;49(6):660-7
references.pmid: 12461451
references.citation: Plast Reconstr Surg. 1979 Nov;64(5):613-21
references.pmid: 504483
references.citation: Exp Neurol. 2003 Sep;183(1):220-31
references.pmid: 12957505
references.citation: Plast Reconstr Surg. 1996 Jan;97(1):139-48; discussion 149-51
references.pmid: 8532772
references.citation: J Reconstr Microsurg. 1999 Feb;15(2):143-9
references.pmid: 10088927
references.citation: Transplantation. 1999 Jul 27;68(2):201-9
references.pmid: 10440388
references.citation: Hand (N Y). 2009 Sep;4(3):239-44
references.pmid: 19306048
references.citation: J Exp Biol. 1981 Dec;95:231-40
references.pmid: 7334319
references.citation: Transplantation. 2004 Aug 15;78(3):383-91
references.pmid: 15316366
references.citation: Transplant Proc. 1990 Oct;22(5):2255-6
references.pmid: 2219361
references.citation: J Neurotrauma. 2001 Feb;18(2):217-29
references.pmid: 11229713
references.citation: Nature. 1977 Aug 25;268(5622):753-5
references.pmid: 895877
references.citation: J Neuropathol Exp Neurol. 2003 Feb;62(2):162-72
references.pmid: 12578226
references.citation: Exp Neurol. 1996 Feb;137(2):301-8
references.pmid: 8635545
references.citation: J Neurosurg. 2010 Jul;113(1):102-9
references.pmid: 19943736
references.citation: J Neurocytol. 1995 Sep;24(9):667-79
references.pmid: 7500122
references.citation: Exp Neurol. 2011 Nov;232(1):7-14
references.pmid: 21763310
references.citation: J Reconstr Microsurg. 2003 Jul;19(5):331-40
references.pmid: 14506582
references.citation: Cell. 1991 Aug 23;66(4):807-15
references.pmid: 1715244
references.citation: Restor Neurol Neurosci. 2000;17(1):39-44
references.pmid: 11490076
references.citation: Exp Neurol. 2007 Sep;207(1):128-38
references.pmid: 17628544
references.citation: Plast Reconstr Surg. 1999 Jun;103(7):1928-36
references.pmid: 10359255
references.citation: J Neurosci. 1994 May;14(5 Pt 2):3231-45
references.pmid: 8182468
references.citation: Neuropathol Appl Neurobiol. 1994 Dec;20(6):587-98
references.pmid: 7898621
references.citation: J Surg Res. 1999 Feb;81(2):201-8
references.pmid: 9927541
references.citation: J Neurocytol. 1989 Oct;18(5):671-83
references.pmid: 2614485
references.citation: Plast Reconstr Surg. 1989 Jun;83(6):1027-36; discussion 1037-8
references.pmid: 2786223
references.citation: Transpl Int. 2011 Aug;24(8):760-9
references.pmid: 21554424