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April 18, 2016

PhillipPopCOLUMBUS, Ohio – Researchers at The Ohio State University Wexner Medical Center and Cincinnati Children’s Hospital Medical Center led a study published online today in the journal Nature Neuroscience that identified an underlying cause of dangerous immune suppression in people with high spinal cord injuries and proposed a possible treatment.

Spinal cord injuries often cause a “paralysis” of the immune system that renders patients more susceptible to pneumonia and other infections. Part of the reason this happens is that the immune system, the body’s defense mechanism against infection, is damaged by spinal cord injury. 

Simple, everyday occurrences that activate normal spinal autonomic reflexes, such as having bowel movements or emptying the bladder, become hyperactive and suppress immune function in people with spinal cord injury.

  “Our new findings show that this immune deficiency develops because hyperactive neural circuitry forms in the injured spinal cord,” said co-lead author Phillip Popovich, professor of neuroscience and director of The Center for Brain and Spinal Cord Repair at Ohio State’s Neurological Institute.  

 “Activation of this hyperactive circuit by simple everyday stimuli, like a full bladder, overwhelms the immune system, killing many of the white blood cells needed to fight infection. Using novel genetic tools, we were able to quiet or silence this hyperactive circuit and reverse the damaging effects that it has on the immune system,” said Popovich.

Using laboratory mouse models, researchers found that profound plasticity develops within spinal autonomic circuitry below high spinal cord injuries, creating an exaggerated sympathetic anti-inflammatory reflex. They also found that chemogenetic silencing of this reflex circuitry blocks the immune suppression that follows spinal cord injury.

“People with spinal cord injuries are more likely to develop fatal infections as the result of their suppressed immune system,” said Yutaka Yoshida, co-lead author and a scientist in the division of Developmental Biology at Cincinnati Children’s. 

In the study, mice with high spinal cord injuries develop atrophied spleens and leucopenia or low white-blood cell counts. In an effort to reverse these immunological deficits, researchers tested chemogenetic agents in the mouse model of spinal cord injury.

Chemogenetics involves experimental engineering of cells so that they express custom-made receptors that will only interact with drugs that are delivered by researchers. When these drugs are injected into mice, they will silence the engineered cells. For mice with high spinal cord injury, researchers silenced signaling pathways in newly formed interneurons that contribute to the exaggerated anti-inflammatory reflex. The chemogenetic silencing successfully reversed this immune system suppressive reflex and reversed atrophy in the animals’ spleens, while increasing white blood cell counts.

“More research is needed before this or similar therapies can be tried in people with spinal cord injuries,” Popovich said.

This research is supported by the National Institute of Neurological Disorders and Stroke and the Ray W. Poppleton Endowment, PRESTO, JSPS Postdoctoral Fellowships for Research Abroad and KANAE Foundation for the Promotion of Medical Science. 

Other researchers involved in the study are Masaki Ueno, Yuka Ueno-Nakamura and Jesse Niehaus from Cincinnati Children’s. Ueno and Niehaus are also affiliated with the Japan Science and Technology Agency.

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Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, 614-293-3737, Eileen.Scahill@osumc.edu