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The Journal of Neuroscience, September 1, 1999, 19(17):7405-7414

Neutralizing Intraspinal Nerve Growth Factor Blocks Autonomic Dysreflexia Caused By Spinal Cord Injury

Natalie R. Krenz^{1, 2, 4}, Susan O. Meakin^{1, 3, 4}, Andrei V. Krassioukov^{1, 2}, and Lynne C. Weaver^{1, 2, 4}

¹ Neurodegeneration Research Group, The John P. Robarts Research Institute, Departments of ² Physiology and ³ Biochemistry, and ⁴ The Graduate Program in Neuroscience, The University of Western Ontario, London, Ontario, N6A 5K8 Canada

Autonomic dysreflexia is a condition that develops after spinal cord injury in which potentially life-threatening episodic hypertension is triggered by stimulation of sensory nerves in the body below the site of injury. Central sprouting of small-diameter primary afferent fibers in the dorsal horn of the spinal cord occurs concurrently with the development of this condition. We propose a model for the development of autonomic dysreflexia in which increased nerve growth factor (NGF) in the injured cord stimulates small-diameter primary afferent fiber sprouting, thereby magnifying spinal sympathetic reflexes and promoting dysreflexia. We identified this population of afferent neurons using immunocytochemistry for calcitonin gene-related peptide. Blocking intraspinal NGF with an intrathecally-delivered neutralizing antibody to NGF prevented small-diameter afferent sprouting in rats 2 weeks after a high thoracic spinal cord transection. In the same rats, this anti-NGF antibody treatment significantly decreased (by 43%) the hypertension induced by colon stimulation. The extent of small-diameter afferent sprouting after cord transection correlated significantly with the magnitude of increases in arterial pressure during the autonomic dysreflexia. Neutralizing NGF in the spinal cord is a promising strategy to minimize the life-threatening autonomic dysreflexia that develops after spinal cord injury.

Key words: spinal cord injury; primary afferent fiber sprouting; autonomic dysreflexia; nerve growth factor; antibody to nerve growth factor; calcitonin gene-related peptide

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19177405-10$05.00/0

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