Nerve cells in the spinal cord activate involuntary, autonomic reflexes often referred to as “fight or flight” responses in response to stressful or dangerous stimuli. These protective responses cause changes in blood pressure and the release of stress hormones into the bloodstream. These responses are usually short-lived and well-controlled. However, this changes after a traumatic spinal cord injury. Now, researchers at the Ohio State University Wexner Medical Center have uncovered that depleting microglia cells prevents abnormal nerve growth that causes long-term illness and impair quality of life.
Their findings are published in Science Translational Medicine in an article titled, “Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice.”
“Robust structural remodeling and synaptic plasticity occur within spinal autonomic circuitry after severe high-level spinal cord injury (SCI),” wrote the researchers. “As a result, normally innocuous visceral or somatic stimuli elicit uncontrolled activation of spinal sympathetic reflexes that contribute to systemic disease and organ-specific pathology. How hyperexcitable sympathetic circuitry forms is unknown, but local cues from neighboring glia likely help mold these maladaptive neuronal networks. Here, we used a mouse model of SCI to show that microglia surrounded active glutamatergic interneurons and subsequently coordinated multi-segmental excitatory synaptogenesis and expansion of sympathetic networks that control immune, neuroendocrine, and cardiovascular functions.”
The study identifies microglia as a potential druggable cellular target that, if controlled properly, could prevent or lessen autonomic dysfunction and improve quality of life for people with spinal cord injury.
“We discovered that exaggerated, life-threatening autonomic reflexes after spinal cord injury are associated with abnormal growth and rewiring of nerve fibers in the spinal cord. A specific cell type, called microglia, controls this abnormal growth and rewiring,” explained corresponding author Phillip Popovich, PhD, professor and chair of the department of neuroscience at the Ohio State University Wexner Medical Center and College of Medicine.
“Using experimental tools to deplete microglia, we found it’s possible to prevent abnormal nerve growth, and prevent autonomic complications after spinal cord injury,” said Popovich, who also is executive director of Ohio State’s Belford Center for Spinal Cord Injury.
“We consider this a major finding,” said first author Faith Brennan, PhD, who began this work at Ohio State and is now a neuroscience researcher at Queen’s University in Kingston, Ontario. “Although this is a well-known consequence of spinal cord injury, research has mostly focused on how the injury affects neurons that control autonomic function.”
Improving autonomic function is a top priority for people living with spinal cord injury. Limiting the effects of dysautonomia after spinal cord injury would significantly increase quality of life and life expectancy, Popovich added.
Looking toward the future, the researchers are focused on identifying the specific neuron-derived signals that control microglia, causing them to remodel spinal autonomic circuitry.
“Identifying these mechanisms could lead to the design of new, highly specific therapies to treat dysautonomia after spinal cord injury. It could also help in other neurological complications where dysautonomia develops, including multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, stroke, and traumatic brain injury,” Popovich said.