Download The central nervous system, or CNS for short, is composed of the

The central nervous system, or CNS for short, is composed of the spinal cord and brain.
Humans have a CNS that is unable to recover and regenerate damaged nerve cells, also named
neurons (Brosamle, et al., 2000). This is caused by chemicals called proteoglycans that are
released by neurons (Cafferty, et al., 2007). Proteoglycans are proteins that have multiple sugars
attached to them, making them resemble a tangled mess (Cafferty, et al., 2007; Krekoski, et al.,
2001). Although they are meant to protect the cells, the proteoglycans’ complex structures make
it hard for neurons to regenerate. They encase the damaged cells and restrain them from growing
through the “wall” of proteoglycans, which is meant to close the damaged site and prevent
further injury. Though it is helpful, it also prevents further growth past this sealed site. Another
molecule, myelin, also gets tangled around the cell, blocking it off from more space to grow into
(Brosamle, et al., 2000). Luckily, recent experiments have shown that regeneration is possible.
By genetically altering, electrically stimulating, and exposing chemicals to cells, proteoglycan
and myelin levels can be lowered. These methods may possibly promote and guide neuronal
regeneration (Al-Majed, et al., 2000; Cafferty, et al., 2007; Davies, et al., 1999).
New research has shown that lowering proteoglycan and myelin levels can promote
regeneration. By reducing the number of proteoglycans around the cells, neurons should then be
able to grow into the new available space. One way to achieve this is by genetically altering the
DNA for specific enzymes, which are molecules that can break proteoglycans (Cafferty, et al.,
2007; Krekoski, et al., 2001; Steinmetz, et al., 2005). DNA for this enzyme was taken from
bacteria and implanted in mice. These mice successfully produced chondroitinase ABC, the
enzyme that breaks proteoglycans. The sugars were taken off of the proteins, creating a less
complex structure (Cafferty, et al., 2007). Because the proteoglycans broke into shorter, smaller
pieces, neurons were able to grow into more areas. Reductions of proteoglycans also allowed
scars in the nerves to reform and completely fill in the damaged areas (Krekoski, et al., 2001).
Scar tissue forming is important to regeneration, because they are the first stages of development
of fully functional cells. Further aid, like that accomplished with chemicals such as zymosan, can
create even better, clearer environments for the neurons (Steinmetz, et al., 2005). In these
experiments, neurons altered to breakdown proteoglycans yielded results of recovery after injury.
Another way to promote regeneration is lowering myelin levels around the cells. Myelin
is a chemical released by neurons to encase themselves, acting like armor against the
environment. However, the “armor” of myelin seals the cell inside. By lowering the amount of
myelin, neurons can grow back into the open space. Lowering myelin levels can be done by
using genetically altered viral enzymes or human anti-bodies (Brosamle, et al., 2000; Tang, et
al., 2007). The DNA of neurons are altered so that viral enzymes and human anti-bodies can be
made and enhanced, respectively. They are able to digest myelin, leaving little restraint on
regeneration. In one study, the human IN-1 antibody was used to break long chains of myelin
around the neurons. Resulting fragments of myelin could not encase the damaged neurons,
allowing them to grow longer (Brosamle, et al., 2000). These severed nerves were able to grow
out into damaged areas and reattach to other nerves. Using genetically altered viruses that release
certain enzymes that facilitate growth is also possible. These were injected around neurons, so
that their enzymes could be near the nerves. The enzymes caused parts of neurons to break
through and grow out of the myelin casing without any myelin covering them (Tang, et al.,
2007). Without any myelin holding the neurons back, they were able to branch out and connect
with other neurons.
Transplanting neurons and surrounding material from another source to the injured area
has also been shown to promote regeneration. Neurons from other nerves were surgically
removed and placed into the damaged site. In the new environment, the neurons grew and
connected to pre-existing broken ones resulting in severed nerves being reconnected (Davies, et
al., 1999). The problem with this is that transplanted nerves grow and attach to any other nerve.
In other words, the wrong nerves will regenerate into the wrong areas. Nerves that communicate
with muscles may grow into the skin, while nerves that interact between the brain and skin may
grow into muscle. Surprisingly, electrical stimulation has been shown to guide nerves during
regeneration and allow them to function correctly. In this approach, nerves are continuously
shocked with pulses of electricity. Any amount of stimulation caused nerves to extend and grow
into the correct areas. With this treatment, sensory nerves grew toward the skin and motor nerves
grew toward muscles successfully (Al-Majed, et al., 2000).
All of these methods may aid large scale human CNS recovery; while on the other hand,
they also have some disadvantages. By genetically altering the nerves, enzymes that break
proteoglycans and myelin will continuously do so. Proteoglycans and myelin are needed by
healthy neurons to protect themselves from injury. If too many are lost, the neurons will be
extremely vulnerable and will not function correctly. The enzymes will have to be modified so
that they can be deactivated/activated when needed. Transplanting neurons from other hosts may
also lead to the rejection of these nerve cells. The body may misjudge them as foreign invaders
and attack them. Even if the neurons are taken from the same host, the surgery to remove them
will cause another area of the body to be damaged. Electrical stimulation may also cause further
damage. If your hands are shocked by static, you feel pain (your response to damage). This
creates the possibility that prolonged electrical shock may injure other neurons. Despite the
setbacks, these new treatments for neuronal regeneration are a huge step for researchers. They
will soon be able to “cure” people with damaged CNS’s and problems like memory loss,
concussions, and paralysis.
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References:
Al-Majed, A. A., Neumann, C. M., Brushart, T. M., & Gordon, T. (2000). Brief electrical
stimulation promotes the speed and accuracy of motor axonal regeneration. Journal of
Neuroscience, 20, 2602-2608.
Brosamle, C., Huber, A. B., Fiedler, M., Skerra, A., & Schwab, M. E. (2000). Regeneration of
lesioned corticospinal tract fibers in the adult rat induced by a recombinant,
humanized IN-1 Antibody fragment. Journal of Neuroscience, 20, 8061-8068.
Cafferty, W. B. J., Yang, S. H., Duffy, P. J., Li, S., & Strittmatter, S. M. (2007).
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Davies, S. J. A., Goucher, D. R., Doller, C., & Silver, J. (1999). Robust regeneration of adult
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Krekoski, C. A., Neubauer, D., Zuo, J., & Muir, D. (2001). Axonal regeneration into acellular
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Steinmetz, M. P., Horn, K. P., Tom, V. J., Miller, J. H., Busch, S. A., Nair, D., Silver, D. J., &
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Tang, X. Q., Heron, P., Mashburn, C., & Smith, G. M. (2007). Targeting sensory axon
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