New research led by The Ohio State University Wexner Medical Center found a potential therapeutic strategy to prevent infections in patients with spinal cord injuries.
This research, published online in the journal Nature Neuroscience, used mice with spinal cord injuries, and breaks new ground in the development of treatments to prevent and reduce the incidence of infections without the use of antibiotics.
The study builds on previous Ohio State-led research that found that spinal cord injury causes the immune system to become “paralysed”, and less able to fight off infections such as pneumonia. Pneumonia is the main cause of death in patients after both acute and chronic spinal cord injury. Decreasing disability infections has a strong impact on the lives of people with spinal cord injury.
“Despite its clinical relevance, the underlying mechanisms of how spinal cord injury causes a systemic immune shut-down are far from being understood. After eight years of work, we were able to identify an entirely new mechanism for how spinal cord injury weakens the immune system,” said principal investigator Jan Schwab, neurologist and physician at Ohio State’s Neurological Institute, who collaborated with researchers from several institutes in Germany.
Researchers demonstrated that susceptibility to spontaneous pneumonia and severe lymphopenia after spinal cord injury resulted from a maladaptive sympathetic-neuroendocrine reflex involving the adrenal glands.
The identification of this two-stage pathological reflex arc – consisting of nerve pathways between the spinal cord and the adrenal glands, as well as a hormone-mediated link with the immune system – helps deepen our understanding of the interconnections between the nervous and immune system.
The discovery of this “immune system paralysis” and its underlying mechanisms represents an important step on the path to improving the treatment of spinal cord injury patients. “Based on our findings, we hypothesise that therapeutic normalisation of the glucocorticoid and catecholamine imbalance in spinal cord injury patients could be a promising treatment strategy,” Schwab said. “This could lead to new treatments to prevent or reduce infections in patients suffering with these injuries without antibiotics, reducing disability and mortality.”
Disrupting nerve fibres to the adrenal glands by high-level but not low-level thoracic spinal cord transection resulted in almost complete suppression of circulating norepinephrine levels and profound stimulation of systemic corticosterone levels. Identical findings were seen in human patients with traumatic complete spinal cord injury, researchers wrote. Given that infections are highly prevalent in spinal cord injured patients, orthodox antibiotic treatments start to lose their effectiveness with time due to the development of resistances.
Caption: Stylised representation of a newly-discovered signaling pathway active after spinal cord injury, which sees the injured central nervous system use adrenal hormone production to potentially disrupt the immune system in a way that lead to severe infections. Credit: Courtesy H Prüss, A Thiriot, The Ohio State University Wexner Medical Center
Source: Ohio State University
Reference: Harald Prüss, and others. Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex. Nature Neuroscience, 2017; DOI: 10.1038/nn.4643