Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol

Introduction Functional outcome following surgical repair in brachial plexus avulsion injury remains poor. Spinal motorneuron death after brachial plexus avulsion injury has been identified as the neurobiological barrier to functional restitution. Post injury oxidative stress reaction, for example...

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Main Author: Sze Kiat, Sim
Format: Thesis
Language:English
Published: 2014
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Online Access:http://eprints.usm.my/39666/1/Dr._Sim_Sze_Kiat_%28Neurosurgery%29-24_pages.pdf
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spelling my-usm-ep.396662019-04-12T05:26:08Z Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol 2014 Sze Kiat, Sim RD520-599.5 Surgery by region, system, or organ Introduction Functional outcome following surgical repair in brachial plexus avulsion injury remains poor. Spinal motorneuron death after brachial plexus avulsion injury has been identified as the neurobiological barrier to functional restitution. Post injury oxidative stress reaction, for example, up-regulation of neuronal nitric oxide synthase (nNOS), not only cause direct damage to the motoneurons, but lead to mitochondrial dysfunction as well, especially the cytochrome c oxidase (CcO) activity, which serve as the main energy generator for neuronal normal activities. Furthermore, the impaired retrograde axonal transport of neurotrophic factors (which are vital for motoneurons survival) secondary to neurofibrogenesis and mitochondrial dysfunction has retarded the neuronal regeneration process. Taxol, a diterpene alkaloid, has the effect in slowing the neurofibrogenesis by microtubule stabilization and facilitate axonal regeneration in rats. This study was designed to evaluate the neuroprotective effect of intrathecally infused Taxol in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury. Material and Method Sprague-Dawley rats were divided into Treatment and Control groups (each group N=32). Brachial root avulsion injury was induced in each rat. The Treatment group received 5 days intrathecal infusion of Taxol (256ng/day) via a micro infusion pump, whereas the Control group received normal saline. Cervical cord was harvested at survival interval of 1 week, 2 weeks, 4 weeks and 6 weeks (n=8 in each subgroup). Number of surviving motoneurons and nNOS-positive motoneurons at injuredventral horn were determined with NADPH-d histochemistry with neutral red counterstaining. Mitochondrial function at the injured ventral horn was measured with CcO histochemistry and densitometer. Independent t-test was applied to detect differences between the study groups at specific survival interval. Results Compared to Control group, the Taxol treated group showed significant reduction in the nNOS expression at 2 weeks, 4 weeks, and 6 weeks, and significantly improved mitochondrial functions at 4 weeks and 6 weeks. The motoneurons survival rate was significantly increased at 2 weeks, 4 weeks, and 6 weeks in Taxol treated rats. Conclusions Taxol has the neuroprotective effect to prevent spinal motoneuron degenaration following brachial plexus avulsion injury by inhibiting nNOS expression and preventing mitochondrial dysfunction. 2014 Thesis http://eprints.usm.my/39666/ http://eprints.usm.my/39666/1/Dr._Sim_Sze_Kiat_%28Neurosurgery%29-24_pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution Universiti Sains Malaysia
collection USM Institutional Repository
language English
topic RD520-599.5 Surgery by region
system
or organ
spellingShingle RD520-599.5 Surgery by region
system
or organ
Sze Kiat, Sim
Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
description Introduction Functional outcome following surgical repair in brachial plexus avulsion injury remains poor. Spinal motorneuron death after brachial plexus avulsion injury has been identified as the neurobiological barrier to functional restitution. Post injury oxidative stress reaction, for example, up-regulation of neuronal nitric oxide synthase (nNOS), not only cause direct damage to the motoneurons, but lead to mitochondrial dysfunction as well, especially the cytochrome c oxidase (CcO) activity, which serve as the main energy generator for neuronal normal activities. Furthermore, the impaired retrograde axonal transport of neurotrophic factors (which are vital for motoneurons survival) secondary to neurofibrogenesis and mitochondrial dysfunction has retarded the neuronal regeneration process. Taxol, a diterpene alkaloid, has the effect in slowing the neurofibrogenesis by microtubule stabilization and facilitate axonal regeneration in rats. This study was designed to evaluate the neuroprotective effect of intrathecally infused Taxol in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury. Material and Method Sprague-Dawley rats were divided into Treatment and Control groups (each group N=32). Brachial root avulsion injury was induced in each rat. The Treatment group received 5 days intrathecal infusion of Taxol (256ng/day) via a micro infusion pump, whereas the Control group received normal saline. Cervical cord was harvested at survival interval of 1 week, 2 weeks, 4 weeks and 6 weeks (n=8 in each subgroup). Number of surviving motoneurons and nNOS-positive motoneurons at injuredventral horn were determined with NADPH-d histochemistry with neutral red counterstaining. Mitochondrial function at the injured ventral horn was measured with CcO histochemistry and densitometer. Independent t-test was applied to detect differences between the study groups at specific survival interval. Results Compared to Control group, the Taxol treated group showed significant reduction in the nNOS expression at 2 weeks, 4 weeks, and 6 weeks, and significantly improved mitochondrial functions at 4 weeks and 6 weeks. The motoneurons survival rate was significantly increased at 2 weeks, 4 weeks, and 6 weeks in Taxol treated rats. Conclusions Taxol has the neuroprotective effect to prevent spinal motoneuron degenaration following brachial plexus avulsion injury by inhibiting nNOS expression and preventing mitochondrial dysfunction.
format Thesis
qualification_level Master's degree
author Sze Kiat, Sim
author_facet Sze Kiat, Sim
author_sort Sze Kiat, Sim
title Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
title_short Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
title_full Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
title_fullStr Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
title_full_unstemmed Inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
title_sort inhibition of neuronal nitric oxide synthase expression and prevention of mitochondrial dysfunction at spinal ventral horn after c7 spinal root avulsion in rats with taxol
granting_institution Universiti Sains Malaysia
granting_department Pusat Pengajian Sains Perubatan
publishDate 2014
url http://eprints.usm.my/39666/1/Dr._Sim_Sze_Kiat_%28Neurosurgery%29-24_pages.pdf
_version_ 1747820764510289920