Targeting the Body’s Immune Response to Improve Recovery After Spinal Cord Injury
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Do you remember climbing a tree as a kid or completing your first cartwheel? Perhaps you are part of the talented few who can perform a standing backflip and spend your weekends impressively performing parkour – which was a hit internet sensation in 2004. At the end of the day, whether you are performing at Cirque du Soleil or simply responding to an email on your cell phone, one thing is certain; your spinal cord is hard at work, actively relaying signals from your brain to your muscles that allow you to perform these finely controlled and intricate movements.
The spinal cord is a long thin tube of nervous tissue that connects your brain to your muscles. In the spinal cord, there are hundreds of thousands of neurons –the fundamental unit of the brain – that carry signals to your individual muscles and subsequently cause your limbs to move. Think of Pinocchio before he came to life. This little marionette had a puppeteer who would pull on strings that would cause Pinocchio’s arms and legs to move. In that way, you can think of the puppeteer as a brain, and the individual strings that moved Pinocchio as the bundle of nerves that form a spinal cord. If Pinocchio’s strings tear, they can be replaced. However, when trauma causes spinal cord injury, recovering the injured neurons, and hence the connection between the brain and peripheral muscles, is not as easy.
The Spinal Cord Injury Team at the University of Western Ontario, led by Drs Arthur Brown and Gregory Dekaban, recently uncovered a potential immunotherapy to treat spinal cord injury by targeting the inflammation that develops as the spinal cord recovers. Inflammation is a normal process within the body where immune cells respond to injury in an attempt to heal and repair damaged tissue. In our case, spinal cord injury is followed by inflammation at the injury site, where the body attempts to repair the torn neurons.
However, if the repair process is not complete and excessive inflammation persists over a prolonged time period, this build-up of inflammation may hinder the repair of damaged tissue. For example, injury to the spinal cord causes neutrophils – a specific immune cell that circulates in blood – to infiltrate the spinal cord and produce excessive inflammation that hinders proper spinal cord repair. This excessive inflammation produces a barrier – in the from of scar tissue – that reduces the severed neurons ability to reconnect with their other halves and obstructs recovery of proper spinal cord function. Think back to the marionette, if the strings that moved the puppets legs were snipped, the legs would no longer move. The spinal cord attempts to put the snipped ends back together, but the scar is in the way. Within the spinal cord, the size of the scar tissue is equivalent to the number of snipped strings (damaged neurons) and may further indicate the extent of damage and the recovery potential.
This research study published in Journal of Neurotrauma in 2012 demonstrated that using an immunotherapy to target neutrophils could dampen the excessive inflammation produced within the damaged spinal cord to help improve healing after spinal cord injury. The immunotherapy consisted of a specific antibody that could recognize and bind to neutrophils to reduce their ability to enter into the injured area of the spinal cord during recovery. Specifically, using a rodent model of spinal cord injury, these researchers demonstrated that in response to this immunotherapy, there were less neutrophils present within the injured spinal cord area at 3 days and 2 weeks after injury. Importantly, the immunotherapy also reduced inflammation and decreased the amount of scar tissue that formed in the spinal cord during recovery.
Another exciting finding from the study was that the immunotherapy lead to an increase in the number of neuronal tracts that surrounded the scar. These neuronal tracts could be thought of as Pinocchio’s snipped strings actively extending out to rewire with their other half. In doing so, the connection between the brain and peripheral muscles is restored, and with it proper motion. The researchers further noted that by reducing neutrophil infiltration and the formation of scar tissue, this immunotherapy was able to improve the movement of the rodents 14 days after injury.
Although promising, adapting these findings to humans still requires further research. The immune system is comprised of a variety of cell types, other than neutrophils, that work together and contribute to inflammation and tissue repair. It is important to also consider how these other immune cells influence spinal cord recovery, and whether they influence this type of immunotherapy. As the authors noted in this paper, spinal cord injuries vary in both severity and amount of inflammation. The immunotherapy studied in this article displayed beneficial effects in a model of severe spinal cord injury and inflammation, but still needs to be tested in less severe injuries with a smaller extent of inflammation.. Nevertheless, this type of research conducted at The University of Western Ontario provides a steppingstone for other researchers interested in targeting the immune system to improve recovery after spinal cord injury.
Original Article: Geremia NM, Bao F, Rosenzweig TE, et al. CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice. J Neurotrauma. 2012;29(3):539-550. https://doi.org/10.1089/neu.2011.1976