Autonomic dysreflexia causes chronic immune suppression after spinal cord injury

Yi Zhang, Zhen Guan, Brenda Reader, Todd Shawler, Shweta Mandrekar-Colucci, Kun Huang, Zachary Wei, Anna Bratasz, Jonathan Wells, Nicole D. Powell, John F. Sheridan, Caroline C. Whitacre, Alexander G. Rabchevsky, Mark S. Nash, Phillip G. Popovich

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Autonomicdysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterizedbyexaggerated activation of spinal autonomic (sympathetic) reflexes, can cause pulmonary embolism, stroke, and, in severe cases, death. People with high-level SCI also are immune compromised, rendering them more susceptible to infectious morbidity and mortality. The mechanisms underlying postinjury immunesuppression are not known. Data presented herein indicate thatADcausesimmunesuppression. Using in vivo telemetry,weshow that ADdevelops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency ofADincreases, there isacorrespondingincrease in splenicleucopeniaandimmunesuppression.Experimentalactivation of spinalsympathetic reflexes in SCI mice (e.g., via colorectal distension) elicits AD and exacerbates immune suppression via a mechanism that involves aberrant accumulation of norepinephrine and glucocorticoids. Reversal of postinjury immune suppression in SCI mice can be achieved by pharmacological inhibition of receptors for norepinephrine and glucocorticoids during the onset and progression of AD. In a human subject with C5 SCI, stimulating the micturition reflex caused AD with exaggerated catecholamine release and impaired immune function, thus confirming the relevance of the mouse data. These data implicate AD as a cause of secondary immune deficiency after SCI and reveal novel therapeutic targets for overcoming infectious complications that arise due to deficits in immune function.

Original languageEnglish (US)
Pages (from-to)12970-12981
Number of pages12
JournalJournal of Neuroscience
Volume33
Issue number32
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Autonomic dysreflexia causes chronic immune suppression after spinal cord injury'. Together they form a unique fingerprint.

  • Cite this

    Zhang, Y., Guan, Z., Reader, B., Shawler, T., Mandrekar-Colucci, S., Huang, K., Wei, Z., Bratasz, A., Wells, J., Powell, N. D., Sheridan, J. F., Whitacre, C. C., Rabchevsky, A. G., Nash, M. S., & Popovich, P. G. (2013). Autonomic dysreflexia causes chronic immune suppression after spinal cord injury. Journal of Neuroscience, 33(32), 12970-12981. https://doi.org/10.1523/JNEUROSCI.1974-13.2013