Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts.
OBJECTIVE
Autologous peripheral nerve grafts are commonly used clinically as a treatment for peripheral nerve injuries. However, in research using an autologous graft is not always feasible due to loss of function, which in many cases is assessed to determine the efficacy of the peripheral nerve graft. In addition, using allografts for research require the use of an immunosuppressant, which creates unwanted side effects and another variable within the experiment that can affect regeneration. The objective of this study was to analyze graft rejection in peripheral nerve grafts and the effects of cyclosporine A (CSA) on axonal regeneration.


METHODS
Peripheral nerve grafts in inbred Lewis rats were compared with Sprague-Dawley (SD) rats to assess graft rejection, CSA side effects, immune responses, and regenerative capability. Macrophages and CD8+ cells were labeled to determine graft rejection, and neurofilaments were labeled to determine axonal regeneration.


RESULTS
SD rats without CSA had significantly more macrophages and CD8+ cells compared to Lewis autografts, Lewis isografts, and SD allografts treated with CSA. Lewis autografts, Lewis isografts, and SD autografts had significantly more regenerated axons than SD rat allografts. Moreover, allografts in immunosuppressed SD rats had significantly less axons than Lewis rat autograft and isografts.


CONCLUSIONS
Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Daniel J
DJ
Hellenbrand
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Katie E
KE
Kaeppler
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Mark E
ME
Ehlers
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Colton D
CD
Thompson
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Joanna C
JC
Zurko
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Morgan M
MM
Buchholz
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Alexandra R
AR
Springer
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Daniel L
DL
Thompson
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Rami K
RK
Ibrahim
a Department of Neurological Surgery , University of Wisconsin , Madison , WI , USA.
Amgad
A
Hanna
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D064596:Isografts / Q000502:physiology; D008297:Male; D025542:Neurofibromin 1 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000601:surgery*; D014184:Transplantation, Homologous / Q000379:methods*
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D025542:Neurofibromin 1; D016572:Cyclosporine
Axonal regeneration; Cyclosporine A; Peripheral nerve injury; Transplantation