CD36 is a pleiotropic receptor involved in several pathophysiological conditions, including cerebral ischemia, neurovascular dysfunction and atherosclerosis, and recent reports implicate its involvement in the endoplasmic reticulum stress response (ERSR). We hypothesized that CD36 signaling contributes to the inflammation and microvascular dysfunction following spinal cord injury. Following contusive injury, CD36-/- mice demonstrated improved hindlimb functional recovery and greater white matter sparing than CD36+/+ mice. CD36-/- mice exhibited a reduced macrophage, but not neutrophil, infiltration into the injury epicenter. Fewer infiltrating macrophages were either apoptotic or positive for the ERSR marker, phospho-ATF4. CD36-/- mice also exhibited significant improvements in injury heterodomain vascularity and function. These microvessels accumulated less of the oxidized lipid product 4-hydroxy-trans-2-nonenal (4HNE) and exhibited a reduced ERSR, as detected by vascular phospho-ATF4, CHOP and CHAC-1 expression. In cultured primary endothelial cells, deletion of CD36 diminished 4HNE-induced phospho-ATF4 and CHOP expression. A reduction in phospho-eIF2α and subsequent increase in KDEL-positive, ER-localized proteins suggest that 4HNE-CD36 signaling facilitates the detection of misfolded proteins upstream of eIF2α phosphorylation, ultimately leading to CHOP-induced apoptosis. We conclude that CD36 deletion modestly, but significantly, improves functional recovery from spinal cord injury by enhancing vascular function and reducing macrophage infiltration. These phenotypes may, in part, stem from reduced ER stress-induced cell death within endothelial and macrophage cells following injury.

Rationale: Spinal cord injury (SCI) may induce significant respiratory muscle weakness and paralysis, which in turn may cause a patient to require ventilator support. Central nervous system alterations can also exacerbate local inflammatory responses with immune cell infiltration leading to additional risk of inflammation at the injury site. Although mechanical ventilation is the traditional treatment for respiratory insufficiency, evidence has shown that it may directly affect distant organs through systemic inflammation. Objectives: This study aimed to better understand the impact of invasive mechanical ventilation on local spinal cord inflammatory responses following cervical or thoracic SCI. Methods: Five groups of female Sprague-Dawley rats were anesthetised for 24 h. Three groups received mechanical ventilation: seven rats without SCI, seven rats with cervical injury (C4-C5), and seven rats with thoracic injury (T10); whereas, two groups were non-ventilated: six rats without SCI; and six rats with thoracic injury (T10). Changes in inflammatory responses were determined in the spinal cord tissues collected at the local site of injury. Cytokines were measured using ELISA. Main results: SCI induced local pro-inflammatory cytokine IL-6 expression for all groups. Mechanical ventilation also had effects on pro-inflammatory cytokines and independently increased TNF-α and decreased IL-1β levels in the spinal cords of anesthetized rats. Conclusion: These data provide the first evidence that mechanical ventilation contributes to local inflammation after SCI and in the absence of direct tissue injury.

Many long-term wheelchair users find themselves unable to accomplish their former daily routines due to fatigue and weakness caused by cardiopulmonary decompensation (CPD). This study showed that long-term survivors of quadriplegia can improve stamina and strength, and therefore participation in daily life occupations, through participation in a regular exercise program using equipment specifically designed for them. Increased aerobic capacity, achieved through regular exercise, has proven with many populations to increase stamina and strength, thereby increasing participation in daily occupations. Whether decompensated survivors of quadriplegia could achieve this was unknown. Until recently there was no way to increase their aerobic capacity due to limited bodily function and lack of accessible fitness equipment. In this study, UPPERTONE, a recently designed fitness system for quadriplegics, was used by six veterans who had survived C-5–C-7 quadriplegia for between 18 and 48 years. They exercised for approximately 45 minutes three times a week for 36 sessions. Baseline level of exercise intensity (weight hefted and number of repetitions as tolerated) and heart rate were recorded and changes were recorded throughout the program. Subjects were interviewed regarding past and present daily life activities. They kept a daily log of activities throughout the study. Using the Canadian Occupational Performance Measure (COPM), subjects were pre-tested, rating their importance of self-identified problems with daily occupations caused by CPD and their performance in and satisfaction with those problem activities. Post-testing showed changes as a result of study participation. Subjects improved COPM scores an average of 7.4 points (greatest 17 points and least 1.5 points), reflecting satisfaction with their ability to perform identified daily activities with less fatigue. Weight hefted increased from an initial average of 22.35 lb. to 52.5 lb. Exercise heart rate increased from an average of 84.8 to 95.2. Subjects were enthusiastic regarding ability to use UPPERTONE independently and their improved quality of life. Clinicians and long-term wheelchair users with a variety of disabilities should understand CPD, its ramifications and the benefits of exercise to this population. Clients who regain ability to care for themselves will enjoy improved quality of life and have less need for long-term care.

Occupational therapy focuses on complex dynamic relationships between people, occupations and environments. For clients with spinal cord injuries (SCI), a way of improving the connection between these three aspects is by providing assistive technology (AT). A fundamental issue identified by consumers regarding AT provision was abandonment, which is caused by a mismatch between aspects of the person, the assistive product, and characteristics of the environment. One solution is engaging collaboratively with clients and recognizing individual needs, thereby allowing therapists to meet clients’ occupational expectations and provide clients with increased functional independence. During this capstone project, barriers to AT provision were identified through an extensive review of the literature, an online survey sent to 82 therapists, and a 90-hour residency with AT specialists. Respondents reported a need for further education on AT, that confidence with high-tech AT was lower than with low-tech AT, and a need for a simplified AT resource tool. This resulted in creation of an educational resource AT tool, in website format, called the Assistive Technology Prescription Tool for Occupational therapists (ATPT-OT). The ATPT-OT is a tool designed to enhance occupational therapists’ ability to identify and recommend AT for individuals with SCI during the prescription process.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20075号 / 医博第4168号 / 新制||医||1018(附属図書館) / 33191 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 林 康紀, 教授 瀬原 淳子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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Introduction: Handcycling is an excellent exercise for people with spinal cord injuries. However, some users experience barriers to transferring to the handcycle. The most common barriers are the height difference between the handcycle and sitting surface and dependence on others. Purpose: This thesis aims to develop an assistive technology to help users independently transfer in and out of a handcycle. Methods: The framework for the thesis is the double-diamond, guiding the designing of the products concepts. Users, professionals, and manufacturers were interviewed regarding the facilitators and barriers while transferring in and out of the handcycle and the product needs to help prevent the barriers. A content analysis was performed to find the facilitators and barriers, and a need analysis was performed to find the needs for the product. The needs were translated into target specifications to have measurable characteristics. Benchmarking was performed, and the products were evaluated in regard to the target specifications. The market segment, personas, mood board, and design brief served to inspire and inform the specifications for the product. Brainstorming and sketching were performed to generate four concepts. The participants evaluated these concepts, and the top-ranked concept was further developed. A computer-aided model was created and rendered to better illustrate the product. A guide on how to use the product was developed based on TAI 4.0, which also was used to find limitations in the transfer technique of the new product. An evaluation regarding the target specifications was also performed. Result: The final product concept allows height transfer and can be used independently. It fulfills seven out of the seventeen target specifications in the current state. However, six target specifications cannot be defined yet as they should be developed further in other iterations. Conclusion: A lifting device concept for transferring was developed. It would still need further iterations to keep improving the product before it would be able to be released for users.