Elsevier

Neuroscience

Volume 108, Issue 4, 18 December 2001, Pages 687-693
Neuroscience

Autonomic dysreflexia in a mouse model of spinal cord injury

https://doi.org/10.1016/S0306-4522(01)00436-5Get rights and content

Abstract

Most experimental studies of spinal cord injury have centered on the rat as an experimental model. A shift toward a mouse model has occurred in recent years because of its usefulness as a genetic tool. While many studies have concentrated on motor function and the inflammatory response following spinal cord injury in the mouse, the development of autonomic dysreflexia after injury has yet to be described. Autonomic dysreflexia is a condition in which episodic hypertension develops after injuries above the mid-thoracic segment of the spinal cord. In this study 129Sv mice received a spinal cord transection at the second thoracic segment. The presence of autonomic dysreflexia was assessed 2 weeks later. Blood pressure responses to stimulation were as follows: moderate cutaneous pinch caudal to the injury (35±6 mm Hg), tail pinch (25±7 mm Hg), and a 0.3 ml balloon distension of the colon (37±4 mm Hg). Previous reports have suggested that small diameter primary afferent fiber sprouting after spinal cord injury may be responsible for the development of autonomic dysreflexia. In order to determine whether autonomic dysreflexia in the mouse may be caused by a similar mechanism, the size of the small diameter primary afferent arbor in spinal cord-injured and sham-operated animals was assessed by measuring the area occupied by calcitonin gene-related peptide-immunoreactive fibers. The percentage increase in the area of the small diameter primary afferent arbor in transected over sham-operated spinal cords was 46%, 45% and 80% at spinal segments thoracic T5–8, thoracic T9–12 and thoracic T13–lumbar L2 respectively.

This study demonstrates the development of autonomic dysfunction in a mouse model of spinal cord injury that is associated with sprouting of calcitonin gene-related peptide fibers. These results provide strong support for the use of this mouse model of spinal cord injury in the study of autonomic dysreflexia.

Section snippets

Spinal cord transection

All protocols for these experiments were approved by the University of Western Ontario Animal Care Committee in accordance with the policies established in the Guide to Care and Use of Experimental Animals prepared by the Canadian Council on Animal Care. Thirteen 129Sv mice (The Jackson Laboratory) weighing between 20 and 30 g were divided into two groups: spinal cord-transected (n=7) and sham-injured (n=6). Anesthesia was induced using 4% halothane and maintained with 1–1.5% halothane in

Presence of autonomic dysreflexia

Two weeks after surgery the spinal cord-transected group was again anaesthetized by halothane. A cannula was implanted in the carotid artery and blood pressure measurements were taken. The average baseline blood pressure was at 80±10 mm Hg and mean blood pressure responses to stimulation were as follows: moderate cutaneous pinch caudal to the injury (35±6 mm Hg), tail pinch (25±7 mm Hg), and a 0.3-ml balloon distension of the colon (37±4 mm Hg) (Fig. 1). As expected, no escape response was

Discussion

To make use of the available spontaneous and engineered mouse mutants in the study of autonomic dysreflexia, we sought to characterize this disorder in wild-type mice. As different mouse strains may respond differently to neurotrauma (Steward et al., 1999), the choice of mouse strain was particularly important. We elected to use 129Sv mice because the majority of engineered mouse mutations have been generated on this genetic background (Simpson et al., 1997). Though graded models of spinal cord

Acknowledgements

This work was supported by the Ontario Neurotrauma Foundation Grant # ONAO 99124. Dr. Arthur Brown is a Research Scholar of the Heart and Stroke Foundation of Canada. Dr. Lynne Weaver was a Career Investigator of the Heart and Stroke Foundation of Canada. We would like to thank Kelly Galloway-Kay for assistance with histological sectioning and Jamie Bruce for assistance with the digital image analysis.

References (47)

  • A.M Strack et al.

    A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections

    Brain Res.

    (1989)
  • A.M Strack et al.

    Spinal origin of sympathetic preganglionic neurons in the rat

    Brain Res.

    (1988)
  • L Weaver et al.

    Changes in immunoreactivity for growth associated protein-43 suggest reorganization of synapses on spinal sympathetic neurons after cord transection

    Neuroscience

    (1997)
  • S.T Wong et al.

    Confocal microscopic analysis reveals sprouting of primary afferent fibres in rat dorsal horn after spinal cord injury

    Neurosci. Lett.

    (2000)
  • J.B Cabot et al.

    Spinal cord lamina V and lamina VII interneuronal projections to sympathetic preganglionic neurons

    J. Comp. Neurol.

    (1994)
  • F.R Calaresu et al.

    Medullary basal sympathetic tone

    Annu. Rev. Physiol.

    (1988)
  • F.S Collins et al.

    New goals for the US. Human Genome Project 1998–2003

    Science

    (1998)
  • J.H Coote et al.

    Reflex discharges into thoracic white rami elicited by somatic and visceral afferent excitation

    J. Physiol.

    (1969)
  • N.G Copeland et al.

    A genetic linkage map of the mouse: current applications and future prospects (see comments)

    Science

    (1993)
  • Corbett, J.L., Debarge, O., Frankel, H.L., Mathias, C., 1975. Cardiovascular responses in tetraplegic man to muscle...
  • W Dietrich et al.

    A genetic map of the mouse suitable for typing intraspecific crosses

    Genetics

    (1998)
  • W Dietrich et al.

    A genetic map of the mouse with 4006 simple sequence length polymorphisms

    Nat. Genet.

    (1994)
  • A Giannantoni et al.

    Autonomic dysreflexia during urodynamics (see comments)

    Spinal Cord

    (1998)
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