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THE EFFECTS OF LONG-TERM SPINAL CORD INJURY ON THE URINARY BLADDER WALL TISSUE MECHANICS

Kevin K. Toosi

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Abstract

Approximately 250,000 - 400,000 individuals in the United States have spinal cord injuries (SCI); urologic complications, including bladder dysfunction, are among the most common problems these patients encounter. Although extensive studies have been conducted on the effects of spinal cord injury on bladder function, the alterations in mechanical behavior and functional properties of the bladder wall tissue and the underlying mechanisms are not well understood. Using a rat model of SCI, it has been previously demonstrated that the bladder wall significantly remodeled in early stages after injury. The remodeling process included changes in mechanical properties, composition and structure of the bladder wall, and occurred as early as 10 days post-injury. Based on the previous findings, it was hypothesized that the altered mechanical environment of the urinary bladder following spinal cord injury was the key signal for the changes in the tissue functional properties. In order to test this hypothesis and gain a better understanding of relationship between function and structure of bladder wall following SCI, the present study combined different experimental methods (including mechanical testing, biochemical assays and histomorphometry) to investigate changes in mechanical properties, as well as alterations in composition and morphology of the bladder wall tissue at various time points up to 10 weeks after injury.Changes in mechanical compliance and material class found during the biomechanical analyses clearly indicated that the bladder wall continuously remodels after spinal cord injury beyond the time point previously tested. The results of histomorphometric study provided first evidence that bladder smooth muscle cells exhibited hypertrophy rather than hyperplasia, corroborated the previous mechanical anisotropy data, and provided the basis for development of structure-based constitutive models for urinary bladder wall tissue. Finally, the findings of biochemical study demonstrated that changes in extracellular matrix of bladder tissue played significant role in bladder functional behavior, and suggested that elastin/collagen ratio might be the key factor in determining the compliance of bladder wall.

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Approximately 250,000 - 400,000 individuals in the United States have spinal cord injuries (SCI); urologic complications, including bladder dysfunction, are among the most common problems these patients encounter. Although extensive studies have been conducted on the effects of spinal cord injury on bladder function, the alterations in mechanical behavior and functional properties of the bladder wall tissue and the underlying mechanisms are not well understood. Using a rat model of SCI, it has been previously demonstrated that the bladder wall significantly remodeled in early stages after injury. The remodeling process included changes in mechanical properties, composition and structure of the bladder wall, and occurred as early as 10 days post-injury. Based on the previous findings, it was hypothesized that the altered mechanical environment of the urinary bladder following spinal cord injury was the key signal for the changes in the tissue functional properties. In order to test this hypothesis and gain a better understanding of relationship between function and structure of bladder wall following SCI, the present study combined different experimental methods (including mechanical testing, biochemical assays and histomorphometry) to investigate changes in mechanical properties, as well as alterations in composition and morphology of the bladder wall tissue at various time points up to 10 weeks after injury.Changes in mechanical compliance and material class found during the biomechanical analyses clearly indicated that the bladder wall continuously remodels after spinal cord injury beyond the time point previously tested. The results of histomorphometric study provided first evidence that bladder smooth muscle cells exhibited hypertrophy rather than hyperplasia, corroborated the previous mechanical anisotropy data, and provided the basis for development of structure-based constitutive models for urinary bladder wall tissue. Finally, the findings of biochemical study demonstrated that changes in extracellular matrix of bladder tissue played significant role in bladder functional behavior, and suggested that elastin/collagen ratio might be the key factor in determining the compliance of bladder wall.

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Available abstract

Approximately 250,000 - 400,000 individuals in the United States have spinal cord injuries (SCI); urologic complications, including bladder dysfunction, are among the most common problems these patients encounter. Although extensive studies have been conducted on the effects of spinal cord injury on bladder function, the alterations in mechanical behavior and functional properties of the bladder wall tissue and the underlying mechanisms are not well understood. Using a rat model of SCI, it has been previously demonstrated that the bladder wall significantly remodeled in early stages after injury. The remodeling process included changes in mechanical properties, composition and structure of the bladder wall, and occurred as early as 10 days post-injury. Based on the previous findings, it was hypothesized that the altered mechanical environment of the urinary bladder following spinal cord injury was the key signal for the changes in the tissue functional properties. In order to test this hypothesis and gain a better understanding of relationship between function and structure of bladder wall following SCI, the present study combined different experimental methods (including mechanical testing, biochemical assays and histomorphometry) to investigate changes in mechanical properties, as well as alterations in composition and morphology of the bladder wall tissue at various time points up to 10 weeks after injury.Changes in mechanical compliance and material class found during the biomechanical analyses clearly indicated that the bladder wall continuously remodels after spinal cord injury beyond the time point previously tested. The results of histomorphometric study provided first evidence that bladder smooth muscle cells exhibited hypertrophy rather than hyperplasia, corroborated the previous mechanical anisotropy data, and provided the basis for development of structure-based constitutive models for urinary bladder wall tissue. Finally, the findings of biochemical study demonstrated that changes in extracellular matrix of bladder tissue played significant role in bladder functional behavior, and suggested that elastin/collagen ratio might be the key factor in determining the compliance of bladder wall.

Key concepts: Spinal cord injury, Urinary bladder, Medicine, Spinal cord, Neurogenic bladder dysfunction, Muscle hypertrophy, Anatomy, Urology

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