According to the National SCI Statistical Center, about 276,000 people in the U.S. currently live with spinal cord injuries, with about 12,500 new cases each year. Spinal cord injury (SCI) research usually focuses on damage to the spinal cord itself and rarely considers the effects of these injuries on the brain.
But a new study by researchers at University of Maryland School of Medicine shows that SCI may lead to brain degeneration. This is the first study to date to show that isolated SCI could result in progressive brain cell loss in key regions in the brain. The research team published their results in two papers, one in The Journal of Neuroscience and the other in Cell Cycle.
The article in The Journal discusses the chronic neuropathic pain mechanisms after rodent SCI, which showed chronic inflammatory changes in the thalamus and in the hippocampus and cerebral cortex.
The researchers studied the effects of mouse SCI cognition, depressive-like behavior, and brain inflammation by administering a battery of tests — including Morris water maze and Y-maze, tail suspension, sucrose preference tests, step-down passive avoidance and novel objective recognition. They found SCI caused spatial and retention memory impairment along with depressive-like behavior in the animal subjects.
Neurological degeneration continued for some time after SCI. Through stereological analyses, the researchers discovered significant neuronal loss in the hippocampus at 12 weeks after the injury, which was not there eight days after the injury. The researchers also found that SCI could initiate a chronic brain neurodegenerative response that may result in physiological depression and cognitive deficits.
In the Cell Cycle article, the scientists examine the effects of isolated thoracic SCI in rats on brain inflammation, cognition and neurodegeneration. This research was groundbreaking in that they showed for the first time that spinal cord injury causes widespread microglial activation in the brain.
The researchers used stereological analysis to expose significant neuronal loss in the cortex, hippocampus and thalamus. They were also able to show that SCI may result in a chronic impairment in the individual's spatial, contextual, retention and fear-related emotional memory.
Building upon their previous work that implicates cell-cycle activation (CCA) in cases of chronic neuroinflammation post-SCI, the researchers analyzed whether CCA contributed to the changes they saw. They found increased expression of cell-cycle-related genes and proteins in the post-SCI hippocampus and cortex.
The scientists also noted that systemic administration of a selective cyclin-dependent kinase inhibitor attenuated the brain inflammation, neuronal loss and cognitive changes after isolated SCI. The researchers say the studies show that the chronic brain neurodegeneration that occurs after SCI relates to microglial activation.
"The brain degeneration was demonstrated in different experimental models and animals," said UM anesthesiology professor and noted neurobiologist Alan Faden, M.D., who led the study. "We also have identified certain molecular mechanisms responsible for these pathological changes and shown that certain drugs can prevent these injuries, including inflammation, brain cell loss, cognitive decline and depressive-like behaviors after injury."
