Nature Neuroscience includes a recent study identifying an underlying cause of immune suppression in patients with high-level spinal cord injuries, and proposing a possible treatment.
In the study, researchers from Cincinnati Children’s Hospital Medical Center and Wexner Medical Center at The Ohio State University write that, in spinal cord injuries higher than thoracic level 5 (T5), a new but abnormal nervous system circuitry starts to form as the body reacts to the spinal cord damage.
Abnormal spinal interneurons activated by the bladder and/or bowel results in the formation of an exaggerated network of neural circuitry that activates an anti-inflammatory and immune suppressive reflex. As a result, people with high-level spinal cord injury develop what is known as spinal cord injury-induced immune suppression syndrome (SCI-IDS), explains a media release from Cincinnati Children’s Hospital Medical Center.
“Infection, a consequence of immune suppression, is the leading cause of death for people with spinal cord injuries,” says Yutaka Yoshida, PhD, co-lead author and a scientist in the Division of Developmental Biology at Cincinnati Children’s Hospital Medical Center, in the release. “Patients and mouse models of spinal injury also are subject to autonomic dysreflexia, a potentially fatal clinical syndrome marked by episodes of high blood pressure.”
Co-lead author Phillip Popovich, PhD, professor of Neuroscience and director of the Center for Brain and at Ohio State, concurs, adding in the release that, “this abnormal spinal cord circuitry likely causes chronic immune suppression and increases the chance that people with spinal cord injuries will suffer from complications caused by common infections, such as pneumonia.”
In an effort to develop a possible treatment to stop immune suppression syndrome, the researchers tested chemogenetic agents in their laboratory mouse models of high-level spinal cord injury. Chemogenetics involves manipulating receptors that are on the surface of cells and either activate or silence these cells. The use of chemogenetics creates the ability to exert very selective pharmacologic control over a variety of cell-signaling processes, the release explains.
Using the mouse models, the researchers used chemogenetics to silence signaling transmissions from newly forming interneurons that trigger the immune suppression reflex. Because the newly forming nerves had specific genetic signatures, the scientists were able to control these neurons using a precisely targeted chemogenetic silencer called hM4Di-DREADD.
According to the release, the researchers report that chemogenetic silencing reversed the immune suppressive reflex in the spinal-injured mice. Atrophy in the animals’ spleens was reversed, and white blood cell counts increased.
[Source(s): Cincinnati Children’s Hospital Medical Center, PR Newswire]