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Title: The inhibition of Leukaemia Inhibitory Factor Enhanced nerve regeneration by the action of the specific Nitric Oxide Synthase II inhibitor Aminoethylisothiourea
Authors: Shakespeare Timothy James
Keywords: rats
LIF protein, human
Leukemia Inhibitory Factor
Nitric Oxide Synthase Type II
sciatic nerve
nerve regeneration
muscle contraction
Myocytes, smooth muscle
Issue Date: Nov-1999
Abstract: Leukaemia Inhibitory Factor (LIF) is a polyfunctional cytokine, which has been shown to enhance nerve regeneration. The mechanism of action of LIF is unknown; however, LIF has been shown to induce superinduction of Nitric Oxide Synthase II (NOS-II) in smooth muscle cells. We investigated whether inhibition of NOS-II alters LIF action on nerve regeneration in vivo. The sciatic nerve of rats was transected at mid-thigh level and repaired by suturing the stumps into each end of a 14mm silicone tube, leaving a 10mm sealed chamber. The tube was filled with 10mg of LIF in Phosphate Buffered Saline (PBS) or PBS alone. Half the rats were injected daily with 3mg/kg body-weight, intraperitoneal, of the specific NOS-II inhibitor aminoethylisothiourea (AET). At 2 weeks, 4 weeks, and 12 weeks post transection, the rats were sacrificed. At 4 weeks the sciatic nerves were fixed in glutaraldehyde, transverse sections were taken 6mm proximal to the proximal end of the tube, at the proximal, middle and distal ends of the tube; and at 6mm distal to the tube. LIF enhanced myelineated axon regeneration, across the chamber compared to PBS. In AET treated groups, axon regeneration was largely absent. At 12 weeks muscle contraction studies were performed and muscle weights compared between the groups. There was no statistically significant difference between the groups; however, the addition of AET for 4 weeks appeared to produce a trend toward lower muscle weights and weaker contractile tetanic forces. This demonstrates that NOS-II plays an important role in axonal regeneration across the chamber at the 4 week time point in our entubation repair model, and may also have a detrimental effect at 12 weeks. Furthermore, this data suggests that LIF may act, at least in part, via NOS-II to enhance nerve regeneration.
Type: Thesis and Dissertation
Affiliates: University of Melbourne, Department of Surgery, St. Vincent's Hospital, Melbourne, Australia
Appears in Collections:Scholarly and Clinical

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