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Neuro-regeneration: New Light on New Life of Nerves The central nervous system (CNS) is composed of the spinal cord and brain. The nervous system is a network of nerves (neurons) that act as wires sending signals from the brain to the body. If these connections are broken, then signals and commands can’t be sent to your limbs. Humans and many other species have CNS’s that are unable to fix these broken connections. The neurons are unable to divide and reconnect with other neurons to reform the “wire” (Brosamle, et al., 2000). This inability is caused by chemicals released by neurons. When damaged; the neurons are encased in a layer of proteins (proteoglycans) that keep them isolated from their environment. This layer is meant to protect the cells by encasing the neurons and acting as a shell or armor. However, the complex structure of these proteins doesn’t allow the neuron to divide past this layer and connect with other neurons. (Cafferty, et al., 2007; Krekoski, et al., 2001). Another molecule called myelin also encases and protects neurons, even when they are healthy. However; it also stops nerves from dividing and reconnecting (Brosamle, et al., 2000). Tests have been made where the levels of these chemicals are lowered. Nerve transplants have also been tested and have shown to cause regeneration (Davies, et al., 1999). These recent experiments have shown that regeneration, or re-growth, is possible. The problem is that if the nerves regenerate, they must regenerate in the correct manner. Damaged and/or transplanted nerves will branch out, but mostly into the wrong areas. Experiments have shown that electrical stimulation can guide regenerating nerves (Al-Majed, et al., 2000). New methods such as genetic therapy, electrically stimulation, and chemical exposure, have shown that neuronal regeneration can be promoted and guided (Al-Majed, et al., 2000; Cafferty, et al., 2007; Davies, et al., 1999). New research has shown that lowering proteoglycan levels can promote regeneration by creating new space for division. One way to achieve this is by genetically altering the DNA (the blueprint of enzymes) for specific enzymes (the machines in cells) that can break down proteoglycans. By changing the “blueprint,” the “machines” will also change. DNA for the enzyme chondroitinase ABC was taken from bacteria, modified to be compatible with mice, and implanted in them. Enzyme cABC broke apart proteoglycans, creating a less complex structure (Cafferty, et al., 2007). Shorter pieces of proteins could not create a shell, and allowed neuron to divide outward. Reduction of proteoglycans also allowed scars to form between severed nerves. Scar tissue forming is important to regeneration, because they are the first stages of development of fully functional cells. Scar cells first form to fill in gaps. Later on, they mature into fully functional neurons (Krekoski, et al., 2001). Without proteins blocking the neurons, they are able to divide and branch outward toward other nerves. In addition to proteoglycan breakdown, scientists have found that myelin breakdown also promotes neuron regeneration. This is done by using genetically altered viral enzymes or human anti-bodies (Brosamle, et al., 2000; Tang, et al., 2007). The DNA for viral enzymes and human anti-bodies were taken and put into mice. These mice produced the enzymes and anti-bodies, which were able to digest myelin. Less myelin left little restraint on regeneration. In one study, the human IN-1 antibody was produced in mice and used to break long chains of myelin around their neurons. Resulting fragments of myelin could not connect and encase the damaged neurons, allowing them to grow longer. The neurons were able to easily grow and reconnect through the broken myelin shell. (Brosamle, et al., 2000). Using genetically altered viruses that release certain enzymes is also possible. Viruses were injected around neurons, and their enzymes caused parts of neurons to break through and grow out of the myelin casing (Tang, et al., 2007). Without any myelin holding the neurons back, they were able to branch out very rapidly and with a large range. Additional methods that do not deal with chemicals include transplanting nerves from another source to the injured area. In mice, neurons from other nerves of another donor were surgically removed and placed into the damaged site. In the new environment, the neurons grew and connected to pre-existing broken ones, connecting severed nerves. The neurons were able to divide successfully, and were fully functional (Davies, et al., 1999). The problem with this is that transplanted nerves attach to any other nerve and possibly grow 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 sensory nerves to grow toward the skin and motor nerves toward muscles successfully (Al-Majed, et al., 2000). All of these methods help human CNS recovery; while on the other hand, they also have some disadvantages. By genetically altering the neurons, 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. Also, prolonged electrical stimulation may possibly damage nerves by electrocuting and injuring 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. Word Count: 987 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). Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. Journal of Neuroscience, 27, 2176-2185. Davies, S. J. A., Goucher, D. R., Doller, C., & Silver, J. (1999). Robust regeneration of adult sensory axons degenerating white matter of the adult rat spinal cord. Journal of Neuroscience, 19, 5810-5822. Krekoski, C. A., Neubauer, D., Zuo, J., & Muir, D. (2001). Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan. Journal of Neuroscience, 21, 6206-6213. Steinmetz, M. P., Horn, K. P., Tom, V. J., Miller, J. H., Busch, S. A., Nair, D., Silver, D. J., & Silver, J. (2005). Chronic enhancement of the intrinsic growth capacity of sensory neurons combined with the degradation of inhibitory proteoglycans allows functional regeneration of sensory axons through the dorsal root entry zone in the mammalian spinal cord. (2005). Journal of Neuroscience, 25, 8066-8076. Tang, X. Q., Heron, P., Mashburn, C., & Smith, G. M. (2007). Targeting sensory axon regeneration in adult spinal cord. Journal of Neuroscience, 27, 6068-6078.
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