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 C5713L/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 C5713L/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.