The role of ErbB inhibitors in promoting nerve regeneration in a mouse model of nerve injury
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Authors
Peller, Jacob
Date
Type
thesis
Language
eng
Keyword
nerve regeneration , nerve injury , ErbB inhibitors , lapatinib , gefitinib
Alternative Title
Abstract
Nerve injury is a common clinical challenge that has a considerable impact on an individual’s quality of life and function. Despite multiple surgical strategies, functional outcomes following nerve injury remain poor. Increasing the rate at which axons regenerate could profoundly improve the success of recovery. The goal of this thesis was to investigate whether the dual ErbB1-ErbB2 inhibitor lapatinib or the ErbB1 inhibitor gefitinib could promote nerve regeneration in both in vivo and in vitro models. Using a mouse transection and repair sciatic nerve injury model, lapatinib was found to increase the number of regenerated myelinated axons at 28 days following nerve repair. For elucidation of the molecular pathway that could be promoting nerve regeneration, in vivo neurite growth assays interestingly demonstrated that gefitinib, more than lapatinib rescued the inhibitory effects by chondroitin sulfate proteoglycan on neurite growth. Furthermore, a mouse forelimb model of nerve injury was characterized which can be used to study the cellular and molecular effects of ErbB inhibitors in transgenic mice. The repurposing of ErbB inhibitors to enhance nerve regeneration requires further study to determine whether this therapy could be translated to improve functional recovery in people with nerve injury.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
CC0 1.0 Universal