Following cervical or upper thoracic level spinal cord injury (SCI), motor, sensory and autonomic systems are disrupted. One form of this autonomic dysfunction is the condition autonomic dysreflexia (AD), which is characterised by episodes of high blood pressure in response to afferent input from regions below the injury level. An animal model of autonomic dysreflexia, the T4 transected rat, was used in this thesis to gain insight into the cardiovascular and temperature components of the disorder, possible peripheral mechanisms and interventions to prevent its development. Chapter 2 of the thesis includes the charaterisation of a T4 transection rat model of spinal cord injury. This characterisation includes confirmation of decreased baseline mean arterial pressure (MAP, 71 down from 117 mmHg) and elevated heart rate (HR, 431 bpm from 366 bpm) for 6 weeks post injury (p.i.). Documentation of the development of AD found that hypertensive responses were fully developed (+20 mmHg) by 4 weeks p.i. Further, during episodes of AD at Weeks 4 and 5 p.i., tail surface temperatures decreased significantly (mid-tail, -1.7oC), indicative of extensive vasoconstriction. Comparison of vascular responses of intact and SCI animals to adrenergic agonists (phenylephrine, PHE and methoxamine, METH) following ganglionic blockade in vivo found that SCI animals experienced prolonged vasoconstriction in blood vessels above and below injury level in response to PHE but not METH. Possible mechanisms of this change included decreased neuronal reuptake of PHE (METH is not a substrate for neuronal reuptake). The presence of prolonged vasoconstriction in blood vessels throughout the body, not just regions below injury level, suggests a widespread mechanism for the change, such as the decreased basal MAP, norepinephrine levels or neural activity present following injury. Thus, it was hypothesised that increased activity from an early stage post injury may prevent the peripheral adaptation and perhaps hinder development of AD. For this, the common rehabilitation technique, treadmill training, was used. Surprisingly, rather than preventing AD, the training actually accelerated its development, producing exaggerated hypertensive responses to colorectal distension (CRD) at Weeks 3 and 4 post-injury (Week 4, Trained: +38.5 ?? 1.5 mmHg; Sedentary: 23.4 ?? 3.1mmHg). Comparison of vascular responses of both groups to PHE injection found no significant difference indicating that the enhanced responses were not a result of peripheral vascular changes. Investigation of the central morphology following SCI, made via immunohistochemical processing of the post-mortem spinal cords, found that Treadmill Trained SCI animals had elevated calcitonin gene related peptide (CGRP) immunoreactivity within lamina III/IV of lumbar segments, compared to intact cords. It is possible that this finding indicates afferent sprouting that may have accelerated the development of AD in Treadmill Trained animals. The results within this thesis highlight the importance of awareness and examination of autonomic function in SCI patients, especially those undergoing rehabilitative training.

Thesis (Ph. D.)--Drexel University, 2007. / Includes abstract and vita. Includes bibliographical references (leaves 111-123).

Thesis (M.A.(Psychology))--University of Pretoria, 2001. / Includes bibliographical references (leave. 175-185).

Magnetic Resonance Imaging (MRI) has been applied in diagnosing Cervical Spondylosis Myelopathy (CSM) clinically. However, morphometric and signal change of MRI have not shown consistent relations with neurological function or outcome after surgical intervention. Diffusion Tensor Imaging (DTI) is an advanced MRI technology, which uses the principle of anisotropic water diffusion property. Recent studies indicated that DTI could be used as diagnostic tools for Cervical Spondylosis Myelopathy (CSM). The study aims to establish a Region of Interest (ROI)-based database. 65 healthy Chinese subjects were recruited for functional MR scanning. The effects on age and gender would also be investigated. Whole cord FA values decreased from upper cord level to lower cord level. White matter FA and AD values are significant higher than grey matter. White matter RD values are significant lower than grey matter. MD values of whole cord, white matter and grey matter are similar. There are no significant differences (P>0.05) of DTI metrics between males and females. There are significant differences (P<0.05) of DTI metrics in cervical spinal cord white matter in advancing age. / published_or_final_version / Orthopaedics and Traumatology / Master / Master of Medical Sciences

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Functional magnetic resonance imaging (fMRI) has become a widely used technique for non-invasive brain mapping, and methods have now evolved to allow fMRI of the spinal cord (spinal fMRI) as well. With the goal of improving spinal fMRI, the studies presented herein have investigated potential sources of noise that might limit its sensitivity and reliability. For example, multiple studies had previously suggested that the majority of structured physiological noise, such as spinal cord motion and cerebrospinal fluid (CSF) flow, appeared to be synchronous with cardiac pulsations. Therefore, we measured cardiac-related spinal cord motion at various levels along the cord, finding that peak anterior-posterior spinal cord displacements often exceeded 0.5 mm throughout the cervical and upper-thoracic regions. On the other hand, we found that cord motion throughout the lower-thoracic, lumbar and sacral levels was consistently small. Based on these findings, we concluded that cord motion is likely to be a significant source of error in spinal fMRI throughout superior, but not inferior, cord regions. Since all motion measurements were acquired at 24 phases of the cardiac cycle, this also allowed us to determine, and subsequently model, the main components of cardiac-related spinal cord motion. By then including these terms in a general linear model (GLM) analysis and reanalyzing 100 previously acquired cervical spinal fMRI datasets, we showed that the sensitivity and specificity were improved by 15-20 % and 5-6 %, respectively, over previous spinal fMRI methods. To push the limits of these improvements, we then carried out the first event-related spinal fMRI study, consistently observing spinal cord responses to 1 s applications of 22 °C thermal stimulation. By measuring these responses at many different phases, we were also able, for the first time, to characterize the impulse response function of SEEP (signal enhancement by extravascular water protons) contrast in the human cervical spinal cord. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2010-08-23 13:35:36.534

No description available.

This study has investigated the role of neurokinin receptors, in particular the NK-1 receptor, in the regulation of excitability of SPN using selective agonists and antagonists. The whole-cell patch clamp technique was used to record from SPN in transverse slices of neonatal rat spinal cord <I>in vitro</I>. Neurones were positively identified as SPN due to their characteristic electrophysiological and morphological properties. Perfusion of the selective NK-1 receptor agonist GR73632 (25 nM-5μM; 2-120 s) induced concentration-dependent depolarising responses in SPN. The response to GR73632 (67% of SPN responsive) was maintained in the presence of TTX (250-500 nM), suggesting that NK-1 receptors are located directly upon SPN. The depolarising response to GR73632 was associated with an increase in neuronal input resistance, reduced with increasing membrane hyperpolarisation, and blocked by two selective NK-1 receptor antagonists, CP-99,994 (1-3 μM) and GR82334 (250 nM-1 μM). Excitatory postsynaptic potentials and strychnine-sensitive inhibitory postsynaptic potentials were also induced by GR73632 in approximately 10% of neurones. Application of GR73632 to a subpopulation of silent SPN induced rhythmical oscillations in membrane potential. The induction of oscillations following NK-1 receptor activation can lead to synchronised action potential firing within groups of SPN. This study has presented preliminary evidence to suggest that a presynaptic NK-1 receptor may exist upon the terminals of neurones which descend from supraspinal centres in synapse upon SPN. Activation of this subtype of NK-1 receptor was found to exert an inhibitory influence upon glutamatergic synaptic transmission to SPN. The results from this study suggest that activation of the NK-1 receptor may have a major excitatory effect upon the activity of SPN, probably by causing the closure of potassium channels open at rest.

This dissertation presents the prediction of quality of life (QoL), composed of by life satisfaction and self-perceived health status, across 5 years post a spinal cord injury (SCI) hospital discharge. Predictor variables of functional independence, pain, and family satisfaction, as mediated by environmental accessibility are examined. Environmental accessibility is conceptualized as being composed of mobility and social integration. Data are a subset from a longitudinal study of adjustment following disability. Two models were examined in order to predict QoL, Model 1 (Life Satisfaction) and Model 2 (Self-Perceived Health Status). Results from this study were obtained by testing models using path modeling. Evaluation indices suggest good to adequate model fit, CFI, RMSEA, and SRMR for Model 1 and Model 2. In Model 1, results indicated that mobility and social integration, components of environmental accessibility, mediated the relationship between functional independence and life satisfaction (beta = 0.243, p = 0.009 and beta = 0.120, p = 0.038, respectively). In Model 2, the component of mobility of environmental accessibility mediated the relationship between functional independence and self-perceived health status (beta = 0.288, p = 0.002). Results indicate that access to the environment is an important predictor of life satisfaction and perceived health status five years after medical discharge for a traumatically-acquired SCI. These factors of environmental access ? mobility and social integration ? appear to be more important determinants of quality of life post-SCI than functional impairment or the presence of pain. Programs that enhance mobility and social integration following return to the community following SCI may be indicated. Furthermore, given that the construct of environmental accessibility is relatively new, studies that examine this construct are needed in order to better understand how it is best conceptualized.

Following cervical or upper thoracic level spinal cord injury (SCI), motor, sensory and autonomic systems are disrupted. One form of this autonomic dysfunction is the condition autonomic dysreflexia (AD), which is characterised by episodes of high blood pressure in response to afferent input from regions below the injury level. An animal model of autonomic dysreflexia, the T4 transected rat, was used in this thesis to gain insight into the cardiovascular and temperature components of the disorder, possible peripheral mechanisms and interventions to prevent its development. Chapter 2 of the thesis includes the charaterisation of a T4 transection rat model of spinal cord injury. This characterisation includes confirmation of decreased baseline mean arterial pressure (MAP, 71 down from 117 mmHg) and elevated heart rate (HR, 431 bpm from 366 bpm) for 6 weeks post injury (p.i.). Documentation of the development of AD found that hypertensive responses were fully developed (+20 mmHg) by 4 weeks p.i. Further, during episodes of AD at Weeks 4 and 5 p.i., tail surface temperatures decreased significantly (mid-tail, -1.7oC), indicative of extensive vasoconstriction. Comparison of vascular responses of intact and SCI animals to adrenergic agonists (phenylephrine, PHE and methoxamine, METH) following ganglionic blockade in vivo found that SCI animals experienced prolonged vasoconstriction in blood vessels above and below injury level in response to PHE but not METH. Possible mechanisms of this change included decreased neuronal reuptake of PHE (METH is not a substrate for neuronal reuptake). The presence of prolonged vasoconstriction in blood vessels throughout the body, not just regions below injury level, suggests a widespread mechanism for the change, such as the decreased basal MAP, norepinephrine levels or neural activity present following injury. Thus, it was hypothesised that increased activity from an early stage post injury may prevent the peripheral adaptation and perhaps hinder development of AD. For this, the common rehabilitation technique, treadmill training, was used. Surprisingly, rather than preventing AD, the training actually accelerated its development, producing exaggerated hypertensive responses to colorectal distension (CRD) at Weeks 3 and 4 post-injury (Week 4, Trained: +38.5 ?? 1.5 mmHg; Sedentary: 23.4 ?? 3.1mmHg). Comparison of vascular responses of both groups to PHE injection found no significant difference indicating that the enhanced responses were not a result of peripheral vascular changes. Investigation of the central morphology following SCI, made via immunohistochemical processing of the post-mortem spinal cords, found that Treadmill Trained SCI animals had elevated calcitonin gene related peptide (CGRP) immunoreactivity within lamina III/IV of lumbar segments, compared to intact cords. It is possible that this finding indicates afferent sprouting that may have accelerated the development of AD in Treadmill Trained animals. The results within this thesis highlight the importance of awareness and examination of autonomic function in SCI patients, especially those undergoing rehabilitative training.