Summary: New research has revealed that the immune response to spinal cord injuries diminishes as individuals age. The study sheds light on the key role the membranes around the spinal cord play in this immune response.
The findings offer hope for the development of treatments that can improve the body’s natural immune response to spinal cord injuries, particularly in older adults. This critical information could lead to improved patient outcomes in the future.
- The immune response to spinal cord injuries weakens as people age.
- The membranes surrounding the spinal cord play a critical role in this immune response.
- These findings could help develop treatments to bolster the body’s immune response, improving outcomes for patients, particularly the elderly.
Source: University of Virginia
New research suggests that the immune system’s ability to respond to spinal cord injuries diminishes with age – and identifies potential avenues to improve that response and help patients heal.
The new findings offer important insights into how the immune system responds to spinal-cord injuries, and why that response becomes blunted with the passing years. Further, it reveals an important role for the membranes surrounding the spinal cord in mounting the immune response to spinal-cord injury.
With this information, doctors one day may be able to bolster the body’s natural immune response to improve patient outcomes, particularly among older adults.
“Recently, it has been reported more aging individuals experience spinal cord injuries. Our findings suggest in aging, there is an impairment in how the immune response is initiated and resolved compared to young,” said researcher Andrea Francesca M. Salvador, who just received her PhD from the University of Virginia School of Medicine.
“Hopefully, our results can help identify points of intervention and druggable targets that can improve recovery and address long-term consequences of injury such as pain.”
Understanding Spinal Cord Injuries
Spinal-cord injuries can have devastating, lifelong effects, leaving patients unable to move, unable to control their bowels or suffering pain, sexual dysfunction or uncontrollable spasms, depending on the severity and location of the injury.
Better understanding how the body responds to spinal-cord injuries is an important step in developing better ways to treat them.
The new findings are the latest from the lab of Jonathan Kipnis, PhD, who made a stunning discovery at UVA in 2015 that the brain was connected to the immune system by vessels long thought not to exist. Prior to this game-changing revelation, the brain had been held to be essentially walled off from the immune system.
The discovery of the unknown vessels in the membranes, or meninges, surrounding the brain rewrote textbooks and opened a whole new frontier in neurological research.
Today, “neuroimmunology,” or the study of the nervous system’s relationship to the immune system, is one of the hottest areas of neuroscience research, and it is poised to transform our understanding of – and ability to treat – a vast array of neurological diseases.
Now Salvador, Kipnis and their collaborators have determined that the meninges surrounding the spinal cord play an essential role in the immune response to spinal-cord injury. They discovered, for example, that previously unknown meningeal lymphatic “patches” form above the site of spinal-cord injuries.
More research is needed to determine exactly what these structures do, but their formation speaks to an important role for the spinal-cord meninges in the immune response to injury.
Further, Salvador and her collaborators quantified how immune cells respond to spinal-cord injuries. They found that this response was much stronger in young lab mice than in older ones, suggesting that scientists may be able to target certain immune cells to improve recovery after spinal-cord injuries.
Together, the findings identify the spinal-cord meninges – and their interactions with other components of the central nervous system – as exciting new areas for researchers to explore as they seek to better understand the body’s complex response to spinal-cord injuries.
“This is an exciting finding and one which may indeed lead to new therapeutic approaches for spinal cord-injury patients,” said Kipnis, now a professor at Washington University School of Medicine in St. Louis and director of its Brain Immunology and Glia Center (BIG Center).
“We are now collaborating with clinicians in a hope to better understand what is happening in human patients and how our findings could be translated to make a real difference.”
The researchers have published their findings in the scientific journal Neuron. The team consisted of Salvador, Taitea Dykstra, Justin Rustenhoven, Wenqing Gao, Susan M. Blackburn, Kesshni Bhasiin, Michael Q. Dong, Rafaela Mano Guimarães, Sriharsha Gonuguntla, Igor Smirnov, Kipnis and Jasmin Herz. The researchers report no financial interests in the work.
Funding: The research was supported by a Howard Hughes Medical Institute Medical Research Fellowship and by the National Institutes of Health, grants AT010416, AG034113, NS096967 and AG057496.
About this spinal cord injury research news
Original Research: Open access.
“Age-dependent immune and lymphatic responses after spinal cord injury” by Andrea Francesca M. Salvador et al. Neuron
Age-dependent immune and lymphatic responses after spinal cord injury
- scRNA-seq reveals age-related immune cell responses after SCI
- Myeloid cell infiltration and diversification is impaired in aged mice after SCI
- A subset of microglia in aged mice displays deficits at steady state and after SCI
- Parenchymal and meningeal myeloid cells facilitate injury-related lymphangiogenesis
Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI.
Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord.
We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury.
Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI.
Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair.