Experimental study on hepatic reinnervation after orthotopic liver transplantation in rats

Background/Aims: The present study examined whether extrinsic hepatic reinnervation occurred after orthotopic liver transplantation (OLT) in rats. Methods: Inbred male Lewis rats were the recipients and females the donors. Tissue specimens were obtained postoperatively from the stump of a recipientʹs hepatoduodenal ligament (A), and the hepatic hilus (B) and peripheral parenchyma (C) of liver allografts, up to 6 months post-operation. Specimens were subjected to immunohistochemical examination using growth-associated protein (GAP)-43 as an axonal marker and transmission electron microscopy (TEM) for observing regenerating axons, as well as the polymerase chain reaction assay to detect the rat sex-determining region Y (SRY) protein gene of the regenerating nerves. Results: At site A, GAP-43-positive nerve axons were identified from day 1 to 1 month post-OLT and SRY protein genes were expressed at and after 3 days post-OLT. At site B, GAP-43-positive axons were observed between 3 days and 1 month, and SRY protein genes were detected at 1 month post-OLT and thereafter. TEM confirmed the presence of regenerating axons at and after 3 days post-OLT. Conclusions: The results demonstrated that regenerating nerve fibers originating from the recipients reinnervated liver allografts. This extrinsic innervation occurred shortly after OLT, and most likely terminated after about 3 months.