Spinal Cord Injury and how to treat it

More than a quarter of a million Americans live with a spinal cord injury (SCI) [1], which occurs when a physical injury damages or severs spinal cord tissue. This injury can break neural connections from the brain to the limbs that are used to initiate voluntary movement, which in extreme cases results in full or partial paralysis. To borrow a description from a previous post, a SCI is like a giant traffic incident on a highway where no cars (neural signals) can get past the site of injury. The extent of the damage depends on the point of the spinal cord that is injured, with injuries higher up on the cord generally resulting in greater loss of function. This blog post will focus on what happens to the injured spinal cord tissue and potential new treatments for SCI patients.

What actually happens in the injury site?

The most obvious consequence of SCIs is that neurons are severed by the physical injury and are no longer able to transmit signals from the brain to the rest of the body (thus blocking the highway). But what happens to the rest of the damaged spinal cord environment?

Within minutes of the injury, blood vessels may rupture and bleed into the spinal cord. Soon after, immune cells, which normally aren’t present in the central nervous system, invade the injury site. In the long term, a scar forms in the spinal cord to seal the injury. When I think of a scar, I think of the numerous scars I can see on my skin due to childhood surgeries and the fact that I am astoundingly clumsy.  These scars helped to replace and close up damaged tissue, for example my knee after epically crashing into a mailbox on a Razor scooter.

Unlike the scars on our skin, the scar that forms in the spinal cord after an injury is made up of two parts: an inner fibrotic scar consisting of extracellular proteins such as collagen (very similar to skin injury scars), and an outer scar made up of a type of cell called astrocytes known as the glial scar. Together, these scars seal the injury and prevent toxins and immune cells from reaching the rest of the spinal cord. Unfortunately, in their attempt to heal, elements of these scars secrete molecules that are known to block axon regeneration, or the regrowth of damaged neurons. Neurons are already unlikely to regenerate in a healthy adult, but when you put a scar in their way that secretes anti-growth molecules, they don’t stand much of a chance.

sci scars

Image adapted from [2]. 24 hours after SCI, the blood-brain barrier (BBB) is disrupted allowing immune cells such as macrophages to infiltrate the spinal cord. Reactive astrocytes begin to surround the injury site. One week after the injury, scar-forming cells secrete extracellular matrix proteins such as collagen to form the fibrotic scar that seals the injury site.

What are potential treatments for SCI?

There are no current cures for SCI, but there are different treatment options for patients with loss of voluntary motor movement. Surgeries to replace damaged nerves and tendons are common and involve moving those that have the best function to the most important muscle groups. For example, at UCSD, tendon transfers can restore some function to over 70% of patients with loss of function in all four limbs [3]! Physical therapy is also common to help build muscle strength where functional connections still exist.

While the therapies described above allow patients to regain some motor function, researchers all over the world are looking for innovative solutions for SCI patients. One promising therapy involves inserting neural stem cells, cells which have the potential to become neurons, into the spinal cord. The idea is that neurons cut by the physical injury can form connections with these new neurons on both sides of the injury, re-establishing some of the connections that were severed. The Tuszynski Lab at UCSD has performed studies where they induced lesions in the spinal cords of monkeys, waited 2 weeks for the injury to begin to seal, and then reopened the injury site to insert human neural stem cells. They found that the monkey neurons were able to form connections with the inserted human stem cells. This increase in connections improved the monkeys’ motor functions, and the study served as an important and promising preclinical trial for stem cell therapies [4].

Other groups are working to electrically stimulate the spinal cord by inserting a device into the spinal cord that emits a continuous electrical current at different frequencies. This device imitates signals coming from the brain to the spinal cord. In 2011 a patient paralyzed from the chest down due to a SCI was able to move paralyzed muscles at will when their electrical stimulator was active [1]! This groundbreaking therapy is now being tested in additional patients and will hopefully become more widely available in the near future.

While we still have a long way to go to treat SCIs, we are definitely making major improvements. It will be interesting to see if the surrounding environment of the injury such as the scar could also be a promising target for treatment. While it was generally assumed that both types of scars block axon regeneration, a recent study has shown that getting rid of the glial scar actually increased axon death following injury [5]. This would suggest that its presence is beneficial for axon regrowth. Hopefully within the next few years we will see even greater advances in SCI research that can further increase patient function and wellbeing.

References

  1.  https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Spinal-Cord-Injury-Hope-Through-Research
  2. Kawano, H. (2012). Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res, 349, 169–180.
  3.  https://health.ucsd.edu/specialties/neuro/specialty-programs/paralysis-center/Pages/spinal-cord-injuries.aspx
  4.  Rosenzweig, E. (2018). Restorative effects of human neural stem cell grafts on the primate spinal cord. Nature Medicine, 24, 484–490.
  5. Faulkner, J. (2004). Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury. Journal of Neuroscience, 24, 2143-2155.
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