People with high-level spinal cord injury develop what is known as spinal cord injury-induced immune suppression syndrome (SCI-IDS). In the study, mouse models of high spinal cord injury have atrophied spleens (a secondary organ that produces white blood cells) and show signs of leukopenia (low white blood cell count).
Co-lead author Phillip Popovich, PhD, professor of Neuroscience and director of the Center for Brain and at Ohio State, said 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. 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.
In the instance of mouse high spinal cord injury 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 (hM4Di-DREADD).
Chemogenetic silencing reversed the immune suppressive reflex in spinal injured mice. Atrophy in the animals’ spleens was reversed and white blood cell counts increased, the researchers report.
The researchers continue to test and refine the use of chemogenetic silencing to treat SCI-IDS. They caution that the experimental treatment method remains years away from testing in people with spinal cord injury.
Also collaborating on the study was first author Masaki Ueno, a member of Yoshida’s lab at Cincinnati Children’s and also the Japan Science and Technology Agency.
—By Nick Miller