Many experimental therapies have been used in the search for effective approaches to improve recovery after spinal cord injury (SCI). One of the most promising approaches is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH-brief exposures to reduced O2 levels alternating with normal O2 levels) elicits plasticity in respiratory and non-respiratory spinal systems in experimental animals. AIH treatment has also been shown to improve walking abilities in persons with chronic incomplete SCI. In this thesis, I first examined the effect of AIH treatment, alone or in combination with motor training, on functional recovery in a rat model of incomplete cervical SCI. Second, I examined the effect of AIH on the expression of plasticity- and hypoxia-related proteins in the spinal cords of SCI rats. In a randomized, blinded, normoxia-controlled study, rats were trained to cross a horizontal ladder and footslip errors were measured before surgery for SCI, 4 wks post-surgery, each day of daily AIH treatment, and 1, 2, 4 and 8 weeks after treatment. dAIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 wks post-SCI. AIH-treated rats made fewer footslips on the ladder task compared to normoxia-treated control rats after 4 days of treatment and this improvement was sustained for 8 wks post-treatment. Importantly, daily ladder training was required for AIH treatment to facilitate recovery. AIH treatment + motor training also increased the expression of Hypoxia-inducible factor-1α (HIF-1α), Vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptors (trkB) and phospho-trkB in spinal motor neurons in SCI rats compared to normoxia-treated SCI rats. In particular these hypoxia- and plasticity-related proteins were differentially expressed both temporally and spatially in the spinal cord during AIH treatment. These findings demonstrate that AIH + motor training can augment neural plasticity and improve motor recovery in an animal model of SCI. Taken together with the promising findings from human SCI studies, the results of this thesis suggest that AIH has potential as an effective therapy to restore motor function after nervous system injury.

SUMMARY Objective of the study. To assess the need of nursing care for patients with spinal cord injury during the early in-patient rehabilitation period. Methods. During the study, thirty-two patients following an acute spinal cord injury, hospitalized in the Neurorehabilitation Unit of the Rehabilitation Division at the Kaunas University of Medicine Hospital, were inquired, examined and cared for. The contingent of studied patients consisted of paraplegic individuals with retained upper limb functions who could fill in themselves a questionnaire, which included 22 questions. Results. The obtained data have shown that 10 women participating in the study were older than 22 men (p £ 0.05): the average age of the women (in the range of 28 to 70 years) was 41 years whereas of the men (in the range of 19 to 52 years), 33.86 years. A reliable correlation according to the Kendall coefficient was determined between the patients self–assessment and the real mobility of the studied individuals. The data of the study have shown that 17 (54.5 percent) of the patients with disturbed urinary function were febrile. The fever was assessed in all 7 patients with continuously indwelled Foley catheters (p £ 0.05), whereas in 15 cases of intermittent catheterization just 5 (33.3 percent) of the patients were febrile (p £ 0.05). The employment of the Fisher criterion has shown that in cases of continuously indwelled Foley catheters for the urinary bladder drainage and the presence of fever... [to full text]

Neuropathic pain is a significant and frequent outcome of spinal cord injury (SCI), and is often refractory to treatment. A better understanding of the pathological processes following injury that contribute to the development of neuropathic pain will aid the search for novel therapeutics. In the second chapter of this thesis a murine model of post-SCI below-lesion neuropathic pain was utilized to investigate changes in GABAergic tone. The gad1:GFP transgenic mouse line allowed the study of a subpopulation of GFPlabeled GABAergic neurons under control of the GABA synthesizing glutamate decarboxylase enzyme. SCI was observed to result in a loss of GABAergic neurons, and secondary markers of GABAergic tone supported this observation. This finding suggests that GABAergic interneuron cell death accounts for the decreased GABAergic tone previously reported post-SCI. In the third chapter of this thesis it was attempted to prevent the death of GABAergic neurons post-SCI using a transgenic mouse line expressing increased levels of the X-linked inhibitor of apoptosis (XIAP) under the ubiquitin C promoter. No differences were observed between ubXIAP and wildtype mice, indicating that increased expression of XIAP is not sufficient to prevent the development of neuropathic pain post- SCI. The fourth chapter of this thesis attempted to prevent the development of neuropathic pain through a novel treatment schedule of the drug pregabalin. Pregabalin administered shortly after SCI prevented the development of neuropathic pain. Pregabalin initiated 1 week post-SCI had no effect. Early pregabalin treatment did not appear to dramatically alter glial activation, or expression of the pregabalin receptor, but we observed changes in markers associated with synaptic plasticity. My findings build upon our knowledge of the mechanisms underlying post-SCI below-lesion neuropathic pain, and suggest new avenues of research, such as the uses of preemptive treatment with pregabalin, that offer promise for translation to clinical use.

Following spinal cord injury (SCI), up to 70% of patients develop a condition known as autonomic dysreflexia (AD). This study investigates the use of Pregabalin as a preemptive treatment to mitigate the development of AD following SCI in an animal model. Saline-treated and dPGB rats (first Pregabalin treatment 7 days post-SCI) demonstrated typical signs of AD, with mean arterial pressure (MAP) increases of 23.5% and 27.4% respectively, following colon distension. In contrast, iPGB animals (first Pregabalin treatment 1 hour post-SCI) had MAP increases of 14.6%; significantly lower than saline-treated animals. Additionally, iPGB animals had significantly lower urine volumes than saline-treated animals on days 9 and 10 post-SCI, indicating a more rapid return of spontaneous bladder voiding. It was concluded that only treatment with Pregabalin immediately following SCI can alleviate large increases in blood pressure that accompany AD episodes. Immunostaining for substance P revealed a significantly higher density in both the dorsal horn and central autonomic area in iPGB animals when compared to saline-treated and uninjured animals, indicating a possible mechanism of sympathetic inhibition following iPGB treatment.

Approximately two-thirds of patients will experience pain following spinal cord injury (SCI). This pain can arise as an immediate consequence of SCI, or can develop over time into chronic, neuropathic pain. Individuals are frequently prescribed opioid analgesics, including morphine, for the treatment of pain in both the acute and chronic phases of SCI. Yet, despite the prevalence of opioid use, no studies have examined the addictive potential of opioids, or their secondary effects, following spinal injury. These experiments used a clinically relevant self-administration paradigm to examine both addiction and functional recovery after morphine administration. To assess morphine administration in the acute phase of SCI, animals were placed in operant chambers 24-hours following spinal injury. In the chambers, depression of a reinforced lever resulted in an intravenous infusion of morphine (or vehicle). Animals were placed in the chambers for 7, 12-hour sessions and could administer up to 30 mg of morphine per session. Morphine self-administration was also examined in the chronic phase of injury. Animals were placed into operant chambers for 7, 12-hour sessions beginning 14 or 35 days after injury. The amount of morphine administered, as well as recovery of locomotor function and general health, was compared across subjects with SCI and sham (no injury) controls. In the acute phase of injury, SCI significantly reduced self-administration of morphine, but administration led to decreased recovery of locomotor function and weight loss. In the chronic phase of injury, self-administration did not differ between contused and sham animals. All subjects administered the full amount of morphine available each day. In this phase of injury, morphine administration led to significant weight loss, but did not attenuate recovery of locomotor function. These studies suggest that spinal injury reduced the addictive potential of morphine in the acute, but not the chronic, phase of SCI. However, acute administration of high doses of morphine decreased recovery of locomotor function. Morphine should not be used in this phase of injury for the clinical treatment of pain. In the chronic phase, opioid use must be closely monitored as use may result in addictive behavior.

No description available.

Compared with our knowledge concerning the responses to exercise of able-bodied athletes there is relatively little known about the exercise responses of athletes who have a spinal cord injury (SCI). The purpose of this thesis was to examine the physiological characteristics of endurance trained wheelchair athletes; to assess the importance of various physiological factors to the endurance performance of wheelchair athletes; to describe and examine the physiological and metabolic responses and performances of wheelchair athletes to endurance and brief high intensity exercise; and to assess the influence of level of SCI or wheelchair racing class on these responses to exercise. The mean peak oxygen uptake (V02 pk) achieved by the group of 27 wheelchair athletes during wheelchair treadmill exercise was 2.11 ±0.53 I. min-1. When the athletes were grouped according to the paralympic racing classification system (TK2; TK3; TK4) the V02 pk values were 1.28 ±0.16 l. min-1,2.10 ±0.43 I. min-1 and 2.32 ±0.52 I. min-1 respectively. The mean peak heart rates of these groups were 112 ±4 b. min-1,190 ±9 b. min-i, and 200 ±9 b. min-1 respectively. The relationship between V02 pk and endurance performance (r=-0.69; p<0.01) was not as high as found between % V02 pk utilised at a given submaximal propulsion speed (r=0.89; p<0.01) or a propulsion speed equivalent to a reference blood lactate concentration (BLA) of 4 mmol. l-1 (r=-0.87; p<0.01). During a 10 km treadmill trial the group of athletes maintained a speed equivalent to 78.4 ±13.6% V02 pk. The TK2 racing class appeared to exhibit lower heart rates and respiratory exchange ratio (R) values throughout the test than the other racing classes. During a one hour endurance test at 80% of top speed (TS), an exercise intensity meaningful to the wheelchair athlete, the group were working at 64.6 ±13.5% V02 pk. The responses observed were indicative of steady state exercise. Oxygen uptake and ventilation rate remained stable, there was no cardiovascular drift, there was a decrease in R value, BLA peaked after 15 minutes and then decreased throughout the remainder of the test. Blood glucose (BGL) concentrations remained similar to the value observed at rest throughout the test. In general, it was found that wheelchair athletes were able to maintain a propulsion speed equivalent 75% V02 pk for prolonged periods of time, irrespective of their level of SCI. There were no differences between the physiological and metabolic responses of the two paraplegic racing classes. The tetraplegic group appeared to exhibit lower heart rates, BLA, BGL and R values throughout the duration of the test. The concentrations of plasma free fatty acid, glycerol, ammonia and urea postexercise indicated a tendency towards higher values in the wheelchair racing class with the lowest lesion level athletes (TK4). During a 20 s high intensity exercise fixed work test there was greater metabolic activity in the TK2 racing class than the TK4 racing class. The metabolic responses of the TK3 racing class to this test were, in general, between these two groups. A 30 s arm sprint resulted in a decrease in power output of greater than 50% for each racing class. The mean power outputs (MPO) generated by the TK2, TK3 and TK4 racing classes were 100.2 ±21.7 W, 188.3 ±48.9 W and 247.2 ±40.3 W respectively. The physiological and metabolic responses showed a similar tendency. A 30 s test at 80% MPO showed that the metabolic responses of each racing class were similar. The results of the thesis suggest that the amount of muscle mass available for recruitment during exercise and the degree of disruption to the sympathetic nervous system play an important role in determining the responses to exercise and the racing performance of wheelchair athletes with a SCI.

Spinal cord injury can result in partial or complete loss of supraspinal control of sympathetic outflow below the lesion. Despite the importance of the sympathetic nervous system in autonomic dysreflexia and orthostatic hypotension, its integrity is not currently assessed in the clinical determination of lesion level - only motor and sensory pathways are examined. The aim of this thesis was to develop non-invasive means of assessing the integrity of sympathetic pathways following human spinal cord injury. Brief innocuous electrical stimuli applied to the forehead evoked cutaneous vasoconstrictor and sudomotor responses in the fingers and toes of able-bodied subjects, which were abolished by complete spinal lesions. Application of these same stimuli to the abdominal wall (below lesion) generated long-lasting cutaneous vasoconstriction (but not sweat release) and significant increases in blood pressure that accumulated with repeated stimuli. Moreover, the magnitude and duration of these spinal somatosympathetic reflexes did not depend on the number of impulses or duration of the sensory input, suggesting that only the initial part of the sensory barrage elicits reflex responses. This work has shown that cutaneous vascoconstriction provides a more robust measure of the integrity of sympathetic pathways than does sweat release. This was confirmed during natural stimulation of somatic afferents during vibroejaculation, which caused marked increases in blood pressure and marked cutaneous vasoconstriction but negligible sweat release below lesion. Muscle vasoconstrictor function below lesion was assessed by asking subjects to perform a maximal inspiratory breath-hold, which is known to cause a sustained activation of muscle vasoconstrictor neurones that counteracts the fall in blood pressure in able-bodied subjects. Blood pressure remained low in paraplegics and, especially, quadriplegics during this manouevre; importantly, heart rate showed a linear increase only in the spinal patients. In the absence of blood pressure measurements, the latter infers an interruption of descending muscle vasoconstrictor pathways. In conclusion, this thesis has demonstrated simple, non-invasive techniques that can be utilised to assess the function of the sympathetic nervous system in spinal cord injury, and highlighted the need to assess the injury in terms of the integrity of the sympathetic nervous system below the lesion level.

Spinal cord injury can result in partial or complete loss of supraspinal control of sympathetic outflow below the lesion. Despite the importance of the sympathetic nervous system in autonomic dysreflexia and orthostatic hypotension, its integrity is not currently assessed in the clinical determination of lesion level - only motor and sensory pathways are examined. The aim of this thesis was to develop non-invasive means of assessing the integrity of sympathetic pathways following human spinal cord injury. Brief innocuous electrical stimuli applied to the forehead evoked cutaneous vasoconstrictor and sudomotor responses in the fingers and toes of able-bodied subjects, which were abolished by complete spinal lesions. Application of these same stimuli to the abdominal wall (below lesion) generated long-lasting cutaneous vasoconstriction (but not sweat release) and significant increases in blood pressure that accumulated with repeated stimuli. Moreover, the magnitude and duration of these spinal somatosympathetic reflexes did not depend on the number of impulses or duration of the sensory input, suggesting that only the initial part of the sensory barrage elicits reflex responses. This work has shown that cutaneous vascoconstriction provides a more robust measure of the integrity of sympathetic pathways than does sweat release. This was confirmed during natural stimulation of somatic afferents during vibroejaculation, which caused marked increases in blood pressure and marked cutaneous vasoconstriction but negligible sweat release below lesion. Muscle vasoconstrictor function below lesion was assessed by asking subjects to perform a maximal inspiratory breath-hold, which is known to cause a sustained activation of muscle vasoconstrictor neurones that counteracts the fall in blood pressure in able-bodied subjects. Blood pressure remained low in paraplegics and, especially, quadriplegics during this manouevre; importantly, heart rate showed a linear increase only in the spinal patients. In the absence of blood pressure measurements, the latter infers an interruption of descending muscle vasoconstrictor pathways. In conclusion, this thesis has demonstrated simple, non-invasive techniques that can be utilised to assess the function of the sympathetic nervous system in spinal cord injury, and highlighted the need to assess the injury in terms of the integrity of the sympathetic nervous system below the lesion level.

This PhD thesis explores the phenomenon of resilience in people with spinal cord injury (SCI). The purpose of this research is to understand how resilience is experienced and given meaning in people with SCI, as well how resilience is fostered, how it impacts upon health and well-being, and how it can be managed to achieve maximum benefits with regard to health and well-being. It is the first in depth narrative investigation of resilience in people with SCI. Using both life story interviews and the process of timelining, participants stories were collected. Following this they were then analysed using dialogical narrative analysis (Frank, 2010, 2012). This enabled participants stories to be examined with regard to their effects on resilience and health and well-being. The analysis shows that firstly, due to the intangible nature of resilience, participants had trouble in articulating exactly what resilience meant to them. Instead, resilience was shown through participants stories which could be grouped into four different narrative types: loss, adaptation, posttraumatic growth (PTG), and life-as-normal. Together, these narrative types constructed resilience, and as such, resilience in people with SCI has four facets or faces , like a four-sided dice. The process of resilience in people with SCI worked by participants drawing upon the different narrative types at different times depending upon the demands being placed upon them. The loss narrative was drawn upon immediately following injury, and was concerned with the narration of the physical, psychological and social losses participants incurred following SCI. The loss narrative fostered resilience by enabling participants to talk about their losses, enabling participants to survive the hardest time of their lives. The second narrative type was the adaptation narrative. This narrative type focussed upon rehabilitation in both the spinal unit and in the community. This narrative type built resilience via progression through rehabilitation towards a quality of life comparable to pre-injury levels. The PTG narrative was concerned with the ways in which participants had developed following SCI and built resilience by shifting the focus onto the positives to come out of participants experiences of SCI. The life-as-normal narrative was used by two participants across their entire life story and enabled participants to continue with their lives with minimal disruption. It built resilience by placing disability in the background and therefore making it unimportant. This thesis then concludes with the empirical, theoretical, methodological and practical implications arising from this research. The potential for resilience to help improve the health and well-being of people with SCI is discussed, as well as the ways in which resilience can have a maximum benefit on health and well-being of people with SCI.