Impact and Mechanisms of Extracellular Electrical Stimulation on Peripheral Nerve Regeneration
| atmire.migration.oldid | 1137 | |
| dc.contributor.advisor | Zochodne, Douglas | |
| dc.contributor.author | Singh, Bhagat | |
| dc.date.accessioned | 2013-07-15T21:31:25Z | |
| dc.date.available | 2013-11-12T08:00:16Z | |
| dc.date.issued | 2013-07-15 | |
| dc.date.submitted | 2013 | en |
| dc.description.abstract | Peripheral nerve injuries are unfortunately very common and debilitating. Peripheral nerve regeneration is slow and regenerative outcomes following severe transection injuries remain limited. Intrinsic inhibitors of neurotrophin signalling diminish the regenerative ability of axotomized neurons and regulate regenerative responses. The overall theme of this thesis is to evaluate whether extracellular electrical stimulation (ES) enhances peripheral nerve regeneration after severe and challenging nerve injuries such as transection and superimposed diabetes, and to understand and exploit its molecular correlates. First, I describe the impact of ES in a severe transection injury model and demonstrate that ES enhances early axon outgrowth that later translates into earlier skin target reinnervation and recovery of sensory and motor function. Utilizing an in-house designed microelectrode array (MEA), I illustrate that ES enhances neurite outgrowth of adult sensory neurons in vitro (Chapter 3). Next, I describe the potential cellular and molecular mechanisms of ES-enhanced regeneration in cultured sensory neurons in vitro and in animal models. Specifically, I observed activation of the PI3-K pathway through downregulation of PTEN expression in response to ES. Other contributing mechanisms involve upregulation of regeneration-associated genes, and enhanced support from perineuronal satellite cells in DRGs (Chapter 4). Finally, in Chapter 5, I show that an ES paradigm has the potential to regenerate axons in a diabetic animal model known for its inherent neuroregenerative deficits (Chapter 5). The results suggest that ES modulates the intrinsic mechanisms of axon regeneration and has a remarkable impact on peripheral neuron plasticity. Overall, the findings support the concept that ES can be utilized as a therapeutic option for severe peripheral nerve injuries. | en_US |
| dc.identifier.citation | Singh, B. (2013). Impact and Mechanisms of Extracellular Electrical Stimulation on Peripheral Nerve Regeneration (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26454 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/26454 | |
| dc.identifier.uri | http://hdl.handle.net/11023/824 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject | Neuroscience | |
| dc.subject.classification | Nerve Regeneration | en_US |
| dc.subject.classification | Electrical Stimulation | en_US |
| dc.subject.classification | Diabetic Neuropathy | en_US |
| dc.title | Impact and Mechanisms of Extracellular Electrical Stimulation on Peripheral Nerve Regeneration | |
| dc.type | doctoral thesis | |
| thesis.degree.discipline | Neuroscience | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Doctor of Philosophy (PhD) | |
| ucalgary.item.requestcopy | true |