Electrical and Optogenetic Stimulation of Sympathetic Neurons to Stabilize Blood Pressure after Acute Spinal Cord Injury

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dc.contributor.advisorPhillips, Aaron
dc.contributor.authorTso, Marcus
dc.contributor.committeememberWhelan, Patrick
dc.contributor.committeememberPatel, Vaibhav
dc.contributor.committeememberPhillips, Aaron
dc.date2023-06
dc.date.accessioned2023-02-01T21:25:23Z
dc.date.available2023-02-01T21:25:23Z
dc.date.issued2023-01-30
dc.description.abstractSpinal cord injury (SCI) is a life-changing condition that results in permanent motor disability and autonomic dysfunction. Acute blood pressure instability is associated with poor long term neurological recovery. Despite current clinical standards of care, blood pressure instability still occurs in the acute phase, and the in-hospital mortality of patients with acute SCI ranges up to 22%. As a result, it is important to examine the mechanisms of blood pressure control in order to identify potential future therapeutic targets for the clinical management of blood pressure instability. A recent study from our team identified regions of the spinal cord that, when stimulated with epidural electrical stimulation (EES), were able to increase blood pressure in spinal cord injured animals. This region was termed the hemodynamic hotspot. Closed-loop application of EES (eSTIM), showed success in stabilizing blood pressure in the chronic phase of SCI in rats. eSTIM induces pressor responses by activating ChAT+ sympathetic preganglionic neurons (SPNs) in the intermediolateral column that innerve the splanchnic vasculature. My thesis aimed to investigate whether blood pressure stability can be restored in mice during the acute phase of SCI using eSTIM, and to develop a method to precisely modulate blood pressure using closed-loop red-shifted optogenetic stimulation to target ChAT+ SPNs. I showed that blood pressure stability is severely disrupted following acute SCI, and that eSTIM can stabilize blood pressure and prevent blood pressure drop during orthostatic challenge in acutely injured mice. I developed a method to stimulate deeper neurons in the spinal cord hemodynamic hotspot using optogenetics and showed that the optogenetic activation of neurons at the hemodynamic hotspot was able to increase blood pressure. The closed-loop optogenetic stimulation of ChAT+ SPNs was able to stabilize blood pressure in the acute phase of SCI. The methods established in this study will pave the way for future studies that aim to investigate the roles of various spinal cord neurons in blood pressure regulation by precise modulation of specific cell subtypes.en_US
dc.identifier.citationTso, M. (2023). Electrical and optogenetic stimulation of sympathetic neurons to stabilize blood pressure after acute spinal cord Injury (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.urihttp://hdl.handle.net/1880/115795
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/40700
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity 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.en_US
dc.subjectSpinal cord injuryen_US
dc.subjectoptogeneticsen_US
dc.subjectneuroprostheticen_US
dc.subjectspinal corden_US
dc.subjectsympatheticen_US
dc.subject.classificationNeuroscienceen_US
dc.subject.classificationMedicine and Surgeryen_US
dc.subject.classificationRehabilitation and Therapyen_US
dc.subject.classificationEngineering--Biomedicalen_US
dc.titleElectrical and Optogenetic Stimulation of Sympathetic Neurons to Stabilize Blood Pressure after Acute Spinal Cord Injuryen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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