Extended survival and function of peripheral nerve allografts after cessation of long-term cyclosporin administration in rats.
To determine whether survival and function of peripheral nerve allografts are possible after cessation of long-term cyclosporin (CsA) treatment, we grafted 4.25 cm Lewis rat peripheral nerve allografts (n = 22) into tibial nerve gaps in recipient brown Norway rats. Allograft groups received CsA (15 mg/kg) subcutaneously every day for 20 days and then biweekly for either 5 or 8 months after transplantation. The control group, brown Norway rats with isografts from brown Norway donor rats (n = 2), also received identical CsA treatment. Semimonthly electrophysiologic studies were done from postoperative week 13 until the animals were killed (up to 79 weeks). The corresponding CsA levels in the nerve and blood were recorded from cessation of CsA up to 58 weeks after surgery. No electrophysiologic signs of rejection were observed in any of the 22 allograft recipients treated with CsA for up to 8 months or in 17 of the 22 observed for up to 58 weeks after cessation of CsA. Overall, 5 of 22 allografts were rejected in the first 8 weeks after discontinuation of CsA. Signs of rejection occurred only in the 5-month treatment group and followed the large initial drop in CsA blood level (from 1010 ng/ml to < 25 ng/ml) that occurred within the first 6 weeks after CsA cessation. The two isograft controls demonstrated no electrophysiologic signs of rejection up to 58 weeks after surgery. Peripheral nerve allografts in the rat can regenerate and function on long-term CsA; after cessation of CsA, they can function for extended periods of time without signs of rejection if trace amounts of CsA are present.(ABSTRACT TRUNCATED AT 250 WORDS)
Frazier
J
J
Division of Orthopaedic Surgery, Bronx-Lebanon Hospital Center, NY 10457.
Yu
L
L
Rhee
E
E
Shaw
L
L
LaRossa
D
D
Rostami
A
A
D000200:Action Potentials; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D006085:Graft Survival; D006614:Hindlimb; D009132:Muscles / Q000294:innervation / Q000502:physiology; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation; D014185:Transplantation, Isogeneic
D016572:Cyclosporine