May 31, 2000

Comm 101
Topic: New ways to aid in nerve regeneration.

General Purpose: To inform
Specific Purpose: To inform the audience about news techniques and mechanisms that aid in nerve regeneration.

Central Idea Statement: The new techniques for nerve regeneration involving magnetic, electrical, and chemical mechanisms look very promising.

INTRODUCTION
I. The site is rather common: someone in a wheel chair unable to use their lower body, or worse, unable to function from their neck down because of an accident. You may even know one of these people. They all have one thing in common: spinal nerve injury. To the majority of us, one of the more famous and recent cases involving spinal trauma is that of Christopher Reeve, known to most of us as Superman. Reeve was riding his horse when he fell off, landed on the back of his head and twisted his neck. His spine was damaged near the second cervical vertebrae; that being two vertebrae away from the base of the skull. He states that after his accident he saw a handbook written in 1990 that didn’t even mention anyone higher than [the fourth cervical vertebrae] because 70 percent of them didn’t live longer than five days. I am very lucky my injury happened at a time when treatment and surgery had improved. Dr. Cotman from UCI, who worked with Reeve says that Reeve remains optimistic that a cure is only a few million dollars away.

II. Prior to the end of the Second World War, if a person survived a severe spinal cord injury, the injury still usually resulted in their early death. This was because of complications that accompanied the injury, such as infections to the kidneys and lungs. Though the development of new antibiotics has greatly improved life expectancy, until recently medical science had not been able to restore nerve function.

III. According to researchers at the University of Alabama using data from the regional SCI Centers, there are 7,800 traumatic spinal cord injuries each year in the US. Yet these numbers do not represent accurate figures since 4,860 per year, die before reaching the hospital. Current estimates are that 250,000-400,000 individuals live with spinal cord injury or dysfunction; forty-four percent of these occur in motor vehicle accidents. More than half of these injuries occur to individuals who are single, and more than 80% of these individuals are male.

IV. Within the last five years, a great many things have been happening in the area of neurological research. Research and treatment involving spinal and nerve injury has progressed considerably. In this speech I will inform you on the new and promising techniques that are currently undergoing testing for human treatment, in terminology that we will be able to understand.

BODY
I. The nervous system consists of the brain, spinal cord, and all branching nerves. There are two parts: the central nervous system, or CNS, and the peripheral nervous system, or PNS. The CNS, consists of the brain and spinal cord, while the PNS involves all the nerves that branch off from the spinal cord to the extremities.

A. When the spine is crushed or bent in an extreme accident, the spinal cord inside is severely bruised and compressed, causing localized injury and death to many of the nerve cells and their fibers. Some of injured nerves fibers survive intact, but lose their electrical insulation, or myelin, over the very short distance of the injury zone. Nerve impulses are blocked at this point.

1. The myelin is the part of the nerve that actually transfers the electrical signal that enables your muscles to move when you want them to move.

B. Nerves regenerate at the rate of about a cm a month. Keep in mind that not all nerves can regenerate (the spinal cord is a prime example) and if a nerve is too damaged or is severed it cannot come back
C. Peripheral nerves will regenerate to a certain extent on their own, but they don’t regenerate over very long distances.

D. The big problem with treating spinal injuries is the fact that mature nerve tissue does not spontaneously regenerate.

II. The three basic ways to treat nerve damage are: first, produce regeneration of the remaining segment of a nerve fiber, or make new connections on the other side of the injury. Second, prevent or rescue the damaged nerve fiber from proceeding on to separation, or perhaps even functionally reunite the two segments, so that both portions of the fiber survive. Or third, facilitate nerve impulse traffic to cross the region of injury in intact fibers where they have lost their electrical insulation.

III. The techniques that are being used to do this involve magnetic, electrical, chemical, or a combination of these to stimulate the damaged nerve.

A. At present surgeons take a nerve from a less important part of the body and transfer it to the site of the injury. Generally the nerve is taken from the lower leg, but then sensation is lost in that portion of the body. Next, the surgeons attempt to repair the nerves by sewing the proximal and distal ends of the nerves together. However, the results are often disappointing. Even with the operation microscope, surgeons are unable to precisely match the thousands of minute axons, each being approximately 1/100 the diameter of a human hair.

B. Arthur Lander, a molecular neurobiologist who came to UCI in 1999 from MIT, does research specifically on neural growth and repair. What scientists currently want to learn, he said, is the fundamental mechanisms that control whether nerve fibers grow and where they grow. It’s not good enough just to get them to grow, you’ve got to get them to connect to the right targets.

C. Dr. Schmidt, Ph.D. from the University of Illinois further states, Imagine the end of a damaged nerve as a small child lost in a forest. The child is resilient and will seek a way out, but she needs the help of a flashlight and a path.

1. Dr. Schmidt recently received a grant from the Whitaker Foundation to research ways to use electricity and an electrically conducting polymer material to stimulate nerve cell growth. Dr. Christine Schmidt’s goal is to give the nervous system’s natural healing mechanism the help it needs in repairing cells. This may mean supplying a tiny burst of electricity to stimulate the growth of a damaged nerve. It also means a pathway or tunnel the growing nerve can follow from the site of the injury to its destination. The path or tunnel Schmidt is hoping will help nerve growth is just that: a minute tube composed of a black-colored material that somewhat resembles Teflon coating. Called polypyrrole, it is a polymer that conducts electricity and can be filled with nutrients that help nerves grow. The chief drawback at present is that polypyrrole is not biodegradable. Schmidt is trying to modify polypyrrole so that it will dissolve into the body and disappear as the nerve regenerates, like biodegradable sutures used in surgery.

D. A recent study performed at Cornell University Medical College has demonstrated that exposure to magnetic fields can result in growth and regeneration of nerves. Dr. Saxena, who was in charge of the research used low-level magnetic fields to trigger growth and regeneration of nerve sections in a culture medium (basically a petri dish). The study also found that those nerves that were not exposed to the magnetic fields experienced nerve degeneration.

1. Dr. Saxena said At the end of the year, we found that included in the new growth was the myelin sheath, a structure responsible for normal nerve conduction of impulses. These findings are especially important because the myelin sheath is the part of the nerve cell that actually conducts the electrical impulses.

E. Another means to restore nerve impulse traffic in both directions through the injured spinal cord is to allow these impulses to cross the regions on the nerve fibers that have been stripped of their insulation, or myelin. The electrical conduction of nerve impulses are blocked at these regions, and though the fiber may be intact, it is still silent. If nerve impulses do not decay in this damaged region, but are conducted to the other side, then they are carried through the rest of the nervous system in a normal fashion. The drug 4 aminopyridine (4 AP) can allow this to happen. The drug was administered by injection, and behavioral improvements could be observed sometimes within 15 minutes. This break through was subsequently moved to limited human testing in two Canadian medical centers with colleagues Dr. Keith Hayes and Dr. Robert Hanseboiut. Their results extended the utility of 4 AP in human quadriplegic and paraplegics.

1. Richard B. Bargains, Director for the Center of Paralysis Research who was present for the administration of the drug said, I particularly remember one man, 5 years after his injury who began to breathe again more normally within ? hour of the administration of the drug. Several more clinical trials of the drug have been completed in the US and Canada.

F. MIT scientists and colleagues have recently discovered a gene that is capable of promoting nerve fiber regeneration. For the first time, they were able to fully reestablish lost connections in the mature brain of a mammal. Although the research was conducted on mice, they believe that it opens the door for the functional repair of brain and spinal cord damage in humans. The scientists have shown that intrinsic genetic factors, not just the tissue environment, are of crucial importance. Brain tissue in adults contains factors that inhibit fiber growth and it lacks growth-promoting hormones. By culturing brain tissue, the scientists determined that genes that cause the growth of nerve fibers shut down at a very young age.

G. Purdue University’s Center for Paralysis Research in conjunction with the School of Veterinary Science are using paraplegic dogs, with their owners consent, to test some new techniques of their own. What researchers do is induce spinal nerve fiber regeneration and to some extent guide it, through the use of an applied electrical field. Very weak electrical fields are a natural part of embryonic development, particularly in the nervous system, and a inherent part of wound healing in animals. In experimental treatment for paraplegic dogs, researchers reverse the polarity of the applied electrical field imposed over the region of the injury every 15 minutes; using an electronic circuit which is implanted securely to the outside of the spine.

H. In the US the use of fetal tissue is a very controversial subject-leading to a presidential ban on any use of human embryonic derived material. Researchers at Purdue University have developed an alternative. They’ve shown that nerve cells removed from the gut and grafted to a spinal cord injury in the same animal can survive. Another interesting and potentially breakthrough technology involves the repair of individual nerve fibers using special chemicals that can both repair and cover holes in nerve membranes and even fuse the two segments of a cut nerve back togther. One may think of this as a molecular-chemical band-aid that prevents injured fibers from preceding on to separation and death.

I. British scientists are developing a pioneering technique for reconnecting severed nerves. But it will only work with peripheral nerves. Researchers at the Royal Free Hospital in London have found a way to persuade the severed ends of damaged nerves to grow though a special tube implanted to bridge the gap. The tiny tubes-a single millimeter in diameter are glued or stitched between the cut nerve ends. The inside of the tubing is coated with special cells, called Schwann cells, which release proteins that encouraged nerve growth. Once the nerve fibers have grown and reconnected the polymer tubing simply dissolves away. The Schwann cells would be grown from the patients’ own cells, taken from a tiny sample of nerve, to avoid rejection problems. Doctors hope to begin implants into patients within a year.

CONCLUSION:
I. The three basic techniques that are currently being used to treat damaged nerves concern electrical, magnetic, and chemical stimulation.

II. Rapid progress is being made in the area of research and treatment involving injured nerves. Within ten years, common place treatment will be available for what is presently deemed to be irreversible spinal cord damage.

Bibliography
BIBLIOGRAPHY
Hibasami H., Hirata H., Morita A., Ohkaya S., Sasaki H., Uchida A. Mechanisms of Nerve Degeneration and Regeneration Abstracts. http://brahms.chem.uic.edu/~cgpage/protocols/cloning.html (18 Sept 1998).

Jacobson Resonance Enterprises, Inc. Jacobson Resonance Enterprises Reports Cornell Study Reveals Nerve Regeneration Possible for the First Time Ever with Jacobson Resonator.

http://www8.techmall.com/199.107.82.50/techdocs/TS981221-8.html (21 Dec., 1997).

Joan Irvine Smith. The Research. http://www.communications.uci.edu/releases/reeve1.html (Spring 1996).

MIT News Office. Scientists ?rebuild’ damaged nerve tissue in mouse brain.

http://www.web.mit.edu/newsoffice/tt/1997/feb26/index.html (15 Feb. 2000)
Mary Lenz. Nerve regeneration project holds hope for injury victims.

http://www.che.utexas.edu/~schmidt/links/neuro.html (29 Sept. 1998).

Richard B. Borgens. New Horizons in the Treatment of Spinal Cord Injury. http://www.vet.purdue.edu/cpr/research.html#Electrical Stimulation (4 Jan 2000).

Thomas Brunshart, M.D.. New Strategies for Nerve Regeneration. www.med.jhu.edu/ortho/news/ws1997/under.html (1997).