Genetic approaches to autonomic dysreflexia.
Autonomic dysreflexia is a potentially life-threatening condition in which episodic hypertension occurs after injuries above the mid-thoracic segments of the spinal cord. Despite the seriousness of this condition, little is known of the molecular mechanisms that lead to its development. The completed sequencing of the mouse genome, its dense genetic map, and the large repository of engineered and spontaneous mouse mutants, make the mouse an ideal model organism in which to study the molecular mechanisms underlying autonomic dysreflexia. We subjected two wild-type strains of mice, 129Sv and C57BL/6, and one spontaneous mouse mutant, Wallerian degeneration slow (Wld s), to spinal cord transection and clip-compression injury. We found that the incidence of autonomic dysreflexia is greatly reduced, compared to spinal cord-transected wild-type mice, in Wld s mice after both injury paradigms and in 129Sv and C57BL/6 that have undergone the clip-compression injury. We also found that the amplitude of the dysreflexic response was greater in cord-compressed 129Sv than in C57BL/6 mice. These results implicate axonal degeneration as an important source of signals that trigger the development of autonomic dysreflexia and are discussed in the context of mouse genetics, interstrain differences and possible molecular mechanisms underlying autonomic dysreflexia after spinal cord injury.
Brown
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Biotherapeutics Research Group, The Spinal Cord Injury Team, Robarts Research Institute and The Graduate Program in Neuroscience, The University of Western Ontario, P.O. Box 5015, 100 Perth Drive, London, ON N6A 5K8, Canada. abrown@robarts.ca
Jacob
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JE
D000818:Animals; D020211:Autonomic Dysreflexia / Q000235:genetics / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D013116:Spinal Cord / Q000033:anatomy & histology / Q000473:pathology; D013117:Spinal Cord Compression; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D014855:Wallerian Degeneration
D015740:Calcitonin Gene-Related Peptide