19 Apr Scientists Turning Off the Immune Suppression Caused by Spinal Cord Injury
MedicalResearch.com Interview with:
Phillip G. Popovich, Ph.D.
Director, Center for Brain and Spinal Cord Repair
Ray W. Poppleton Research Designated Chair
Department of Neuroscience
Wexner Medical Center at The Ohio State University
Columbus, Ohio 43210
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Popovich: People that suffer a spinal cord injury (SCI) at a high spinal level (e.g., cervical SCI), are at increased risk for developing autonomic dysreflexia (AD), a potentially life-threatening condition of sudden onset high blood pressure.
In people and animals with SCI, reflexes that are activated by routine stimuli including filling of the bladder or bowel often trigger AD.
We recently found that these same reflexes also suppresses the immune system (see Zhang et al., 2013; PMID 23926252)
Since people with high level spinal cord injury also are at increased risk for developing infections (e.g., pneumonia), we set out to understand how SCI changes the autonomic circuitry in the spinal cord that controls immune function.
We found that after a period of one month, the number of connections between spinal cord interneurons and autonomic neurons that directly control immune function increases dramatically.
Also, this newly formed circuitry is “hyperactive” and discharge of neurons in this circuit causes hormones to be released into the blood and immune organs that overstimulate immune cells, causing them to die.
Fortunately, we were able to show that the hyperactive spinal cord circuitry can be silenced. We used a novel technique known as “chemogenetics” to silence excitatory interneurons in the aberrant circuit. When the circuitry was silenced, immune cells were protected in spinal cord injury mice.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Popovich: Autonomic complications of high level spinal cord injury including inability to control cardiovascular reflexes and immune suppression have been difficult to treat, mostly because the mechanisms causing these complications have not been defined.
Our new data show that after high level SCI in mice, the spinal cord reorganizes, creating new circuitry. This “rewiring” takes time, evolving over many weeks. Similar changes are likely in humans.
Whether chemogenetics or similar intervention(s) can be used to manipulate spinal cord autonomic circuitry in humans will require additional research. However, data from our study provide a “blueprint” that may explain why the frequency of AD and infectious complications increase in some people living with spinal cord injury.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Popovich: We still do not understand why spinal cord injury does not cause AD or immune suppression in all individuals, even in those that are affected by high level SCI.
We also need to understand how and why spinal cord circuit rewiring occurs and when it does, are there critical periods during which interventions will work better? For example, can we block the rewiring?
We show that tremendous plasticity develops within autonomic circuitry controlling immune organs. Does a similar type of reorganization develop inother neuronal networks controlling other organs and how does the autonomicplasticity affect motor and sensory functions? Is there cross-talk between these different modalities that are affected by circuit rewiring?
Finally, for those in which the rewiring has already been established for many years, is it possible to reorganize this circuitry using existing drugs or rehabilitation therapies and will such interventions affect AD and immune function?
Masaki Ueno, Yuka Ueno-Nakamura, Jesse Niehaus, Phillip G Popovich, Yutaka Yoshida. Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury. Nature Neuroscience, 2016; DOI: 10.1038/nn.4289