Autonomic Dysreflexia Causes Chronic Immune Suppression after Spinal Cord Injury

Abstract

Autonomic dysreflexia (AD), a potentially dangerous complication of high-level spinal cord injury (SCI) characterized by exaggerated 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 immune suppression are not known. Data presented herein indicate that AD causes immune suppression. Using in vivo telemetry, we show that AD develops spontaneously in SCI mice with the frequency of dysreflexic episodes increasing as a function of time postinjury. As the frequency ofADincreases,thereisacorrespondingincreaseinsplenicleucopeniaandimmunesuppression.Experimentalactivationofspinalsympathetic 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.

Evidence-based scientific exercise guidelines for adults with spinal cord injury: an update and a new guideline

“…This guideline has been translated into over a dozen languages, distributed and adopted internationally, and proven efficacious for improving fitness in adults with SCI [21]. A limitation, however, is that it does not specifically address cardiometabolic health, which encompasses measures of body composition (e.g., fat mass, lean body mass) [22,23] and risk factors for cardiovascular disease (e.g., blood lipids and cardiac vascular structure/function) [24][25][26]. A lack of highquality research evidence regarding the effects of PA on health outcomes precluded the formulation of a cardiometabolic health guideline in 2011 [19].…”

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

“…This is in contrast to previous work showing more severe effects after higher-level injuries on autonomic dysreflexia, inflammation, and cardiovascular problems. 16,66,67 Both injury levels used here, however, completely (cervical) or partially (thoracic) disrupt descending control of sympathetic neurons innervating the liver and, thus, differences in hepatic changes between cervical and thoracic injuries were subtle. To further test this, a cohort of animals received a lumbar SCI to spare sympathetic innervation to the liver.…”

Autonomic Consequences of Spinal Cord Injury

“…Novel methodologies to detect spontaneous autonomic dysreflexia in experimental SCI rodents have been developed with telemetric monitoring techniques (282,387). Together with colon or bladder distension models, the refined analytical tool using algorithms to detect spontaneous events represents a clinically relevant approach to evaluate pharmacological therapeutic intervention for autonomic dysreflexia.…”