Pierre-Yves Mure1, Mark Galdo, Nathalie Compagnone. 1. Department of Neurological Surgery, Brain and Spinal Injury Center, Laboratory for Spinal Cord Development and Regeneration, University of California at San Francisco, California 94143-0527, USA.
Abstract
OBJECT: The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. METHODS: A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. CONCLUSIONS: The authors found that early recovery of controlled voiding is predictive of motor recovery.
OBJECT: The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. METHODS: A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. CONCLUSIONS: The authors found that early recovery of controlled voiding is predictive of motor recovery.
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