No Two Spinal Cord Injuries are the Same
No two spinal cord injuries are the same. Two people with the same level and grade of injury may have very different functional capabilities. In an uninjured state, the system that controls movement of the body (motor system) is incredibly complex, and countless signals from the brain, as well as the spinal cord, contribute to the generation of voluntary movements. After spinal cord injury (SCI), this system becomes even more complicated when some important structures and pathways become damaged, while others remain intact.
The inherent complexity and injury-induced variability that results from injury to the motor system can make treatment and recovery difficult. After SCI, we all know that “one size does NOT fit all.” However, in this case, complexity may also afford opportunity. Widespread distribution and functional complexities within the spinal cord may actually offer an increased number of potential targets for improving function within the central nervous system.
Identifying those targets is the key. Thus far, attempts to effectively map the complex network that composes the motor system have been largely incomplete. In an effort to better understand how the brain is connected to the spinal cord, scientists at The Miami Project, led by Dr. Pantelis Tsoulfas, Associate Professor, partnered with scientists from Marquette University to utilize a newly developed and powerful research tool. Retrograde viral vectors are able to move viruses along nerve fibers in the “opposite” direction, from termination of the nerve fiber (synapse) to its point of origination at the cell body (soma). They used AAV2-Retro, an adeno-associated virus that has been mutated to deliver genetic material to the cells it infects. The scientists injected AAV2-Retro into the spinal cords of rats, with and without spinal cord injuries, at different levels (cervical and lumbar).
In order to visualize the neurons and their pathways, the team used special methods to “clear” the tissue, making it transparent, and highlight the areas infected by the viral vector, using fluorescent markers. Finally, 3D microscopy enabled the visualization of interconnected networks, made up of cell bodies and their projections, in the central nervous system.
What they saw under the microscope was nothing short of amazing. The researchers were able to see intricate networks of connectivity between the spinal cord and different areas of the brain, including the brainstem, midbrain, and cortex. Within three days of injection, some important pathways, including the corticospinal tract, were clearly visible within intact tissue. Complex branching structures lit up in fluorescence and the microscopic roadmaps between the brain and the spinal cord could be appreciated in fine detail.
To further our understanding that no two spinal cord injuries are alike, powerful research tools, like AAV2-Retro, are revolutionizing scientific discovery within the central nervous system. Researchers can now investigate what types of, and how many, neural pathways are necessary for generating voluntary movements after SCI. Retrograde viral vectors may offer an opportunity for therapeutic gene delivery to a wide distribution of neural networks involved in movement control. In turn, these targeted approaches may lead to increases in motor output and improved quality of life in people with SCI.
Wang Z, Maunze B, Wang Y, Tsoulfas P, Blackmore MG. (2018). Global Connectivity and Function of Descending Spinal Input Revealed by 3D Microscopy and Retrograde Transduction. J Neurosci. 5;38(49):10566-10581.