QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 15, 2006, 26(11):2923-2932; doi:10.1523/JNEUROSCI.4390-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Cameron, A. A. Articles by Rabchevsky, A. G. Search for Related Content PubMed PubMed Citation Articles by Cameron, A. A. Articles by Rabchevsky, A. G.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Genetic Manipulation of Intraspinal Plasticity after Spinal Cord Injury Alters the Severity of Autonomic Dysreflexia

Adrian A. Cameron,¹ George M. Smith,^1,2 David C. Randall,^1,2 David R. Brown,² and Alexander G. Rabchevsky^1,2

¹Spinal Cord and Brain Injury Research Center and ²Department of Physiology, University of Kentucky, Lexington, Kentucky 40536

Correspondence should be addressed to Dr. Alexander G. Rabchevsky, University of Kentucky, Spinal Cord and Brain Injury Research Center, B371, Biomedical and Biological Sciences Research Building, 741 South Limestone Street, Lexington, KY 40536-0509. Email: AGRab{at}uky.edu

Severe spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia, which is often triggered by painful distension of pelvic viscera (bladder or bowel) and consequent sensory fiber activation, including nociceptive C-fibers. Interruption of tonically active medullo-spinal pathways after injury causes disinhibition of thoracolumbar sympathetic preganglionic neurons, and intraspinal sprouting of nerve growth factor (NGF)-responsive primary afferent fibers is thought to contribute to their hyperactivity. We investigated spinal levels that are critical for eliciting autonomic dysreflexia using a model of noxious colorectal distension (CRD) after complete spinal transection at the fourth thoracic segment in rats. Post-traumatic sprouting of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent fibers was selectively altered at specific spinal levels caudal to the injury with bilateral microinjections of adenovirus encoding the growth-promoting NGF or growth-inhibitory semaphorin 3A (Sema3a) compared with control green fluorescent protein (GFP). Two weeks later, cardio-physiological responses to CRD were assessed among treatment groups before histological analysis of afferent fiber density at the injection sites. Dysreflexic hypertension was significantly higher with NGF overexpression in lumbosacral segments compared with GFP, whereas similar overexpression of Sema3a significantly reduced noxious CRD-evoked hypertension. Quantitative analysis of CGRP immunostaining in the spinal dorsal horns showed a significant correlation between the extent of fiber sprouting into the spinal segments injected and the severity of autonomic dysreflexia. These results demonstrate that site-directed genetic manipulation of axon guidance molecules after complete spinal cord injury can alter endogenous circuitry to modulate plasticity-induced autonomic pathophysiology.

Key words: nerve growth factor; semaphorin 3A; sprouting; sympathetic; neurotrophin; autonomic

---

Received March 21, 2005; revised Nov. 22, 2005; accepted Jan. 25, 2006.

Correspondence should be addressed to Dr. Alexander G. Rabchevsky, University of Kentucky, Spinal Cord and Brain Injury Research Center, B371, Biomedical and Biological Sciences Research Building, 741 South Limestone Street, Lexington, KY 40536-0509. Email: AGRab{at}uky.edu

This article has been cited by other articles:

				X.-Q. Tang, P. Heron, C. Mashburn, and G. M. Smith Targeting Sensory Axon Regeneration in Adult Spinal Cord J. Neurosci., May 30, 2007; 27(22): 6068 - 6078. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help