Nerve cells transmit and receive information traversing the human body in the form of electrical impulses. These extremely delicate and sensitive cells are easily damaged as a result of accidents or disease. Following impairment, their likelihood of regaining function largely depends on their anatomical location. Nerves in the limbs and torso, for example, are able to repair themselves and regain some function.
Neurons in the brain and spinal cord, however, do not have these regenerative capabilities. Here, their healing is hindered by excessive scar tissue formation and inhibitory molecular processes inside the nerves. Consequently, around 40 percent of individuals with spinal cord injuries are considered paraplegic, and 60 percent are quadriplegic.
What are the cellular and molecular changes during spinal cord injury that are frustrating regeneration? Could the involvement of inflammatory processes be doing more harm than good?
Jonathan Kipnis and Kodi Ravichandran from the University of Virginia School of Medicine are seeking answers to these and other unanswered questions which could serve as a foundation for spinal cord injury therapies. The work is part of a $14 million grant to support research on inflammation from the Chan Zuckerberg Initiative.
In particular, the scientists are interested in the role that phagocytes play in the spinal cord injury response. These cells act like “cleaning crews” at the site of tissue damage, engulfing and removing dead cells and debris. Still unknown is whether spinal cord neurons fail to regenerate because phagocytic cells called microglia are unable to penetrate the damaged tissue to work their magic.
Previous studies have shown that microglia migrate rapidly to the location of tissue damage in the spinal cord and create a protective scar. Their interplay with other inflammatory cells during this process remains obscure, though new fluorescent microscopy methodologies as used by the team at University of Virginia could change this.
According to the researchers, understanding the dynamics of phagocytic cells through single-cell analyses can inform therapeutic strategies. Knowing what cell type is the phagocyte at the site of damage would allow us to specifically target that cell type or subtype of cells to eat more of the cellular debris after the brain or spinal cord injury, says Ravichandran.
“Plus, via these single-cell analyses, we will also learn how the genetic program of the ‘cleaning crew’ changes at the injury site over time, and this would help us to mold the response toward better tissue repair.”
Originally published at https://www.labroots.com on May 2, 2020.