Nerve Regeneration

This website explores four biotechnological approaches to nerve regeneration: stem cell therapy, guidance channels, neurotrophic factors, and gene therapy.

What is the central nervous system?

At the core of the human nervous system, a control system of the body, is the central nervous system (CNS), which is composed of the brain and spinal cord. Using electrical signals that travel from the CNS through the peripheral nervous system (PNS), the brain controls effector cells, which carry out the physiological responses "requested" by the brain. Thus, the nervous system is a "wired" communication system of the body.

Anatomically, the fundamental cell of the brain is the neuron, which consists of a cell body, branch-like extensions off the cell body called dendrites, and at least one longer extension off the cell body called an axon. The dendrites conduct signals from their tips toward the neuron cell body whereas the axon carries messages away from the cell body toward the terminal end of the axon. The neuron communicates with other cells, such as effector cells, through the distal tips of the axon.


Diagram of a neuron.
Source: http://www.ccs.neu.edu/groups/honors-program/freshsem/19951996/cloder/neuron.html

Nerves are bundles of axons from different neurons that carry signals in the same direction; nerves are the essential intermediary connecting the brain to effector cells. Thus, if nerves are severely damaged, the signal between the cell body and effector cells is interrupted, and neurons are unable to convey effective "requests," such as a muscle movement. This is similar to cutting an electrical cord connecting a lamp to an outlet.


Diagram illustrating the spinal nerves and their function
Source: http://www.spinalinjury.net/html/_spinal_cord_101.html

What damages nerves?

Nerves can be damaged either through trauma or disease. Nerve trauma may be incurred through motor vehicle accidents, severe falls, lacerations, and typing. Traumatic nerve injury, such as carpal tunnel syndrome, is caused by the compression of nerves. Other trauma, such as falls and motor vehicle accidents, may lead to the severance of nerves. Diseases that damage nerves include multiple sclerosis, diabetes, spina bifida, and polio. Multiple sclerosis, for example, causes the breakdown of the insulating myelin surrounding axons.

The most dramatic and serious nerve damage occurs to the spinal cord. Damage to the lower spinal column may lead to paraplegia, paralysis of the lower extremities, and damage to the upper spinal column may lead to quadriplegia, paralysis of all four extremities. The incidence of spinal cord injury in the US is 11,000 per year and the prevalence is 250,000 to 400,000. The cost to support a patient with a spinal cord injury through his or her lifetime is estimated to cost between $400,000 to $2.1 million depending on the severity of injury.

Actor Christopher Reeve's well-publicized horse riding accident in 1995, which led to his becoming quadriplegic, has recently brought national attention to the debilitating effects of spinal cord injury. Following his accident, The Christopher Reeve Paralysis Foundation was established to fund research for paralysis.

Why can't the CNS heal damaged nerves itself?

Unlike a cut that heals, the central nervous system has limited ability to fix its damaged nerves, in contrast to the peripheral nervous system. When parts of the central nervous system are critically injured, the CNS cannot generate new neurons nor regenerate new axons of previously severed neurons. Severed CNS tips initially try to grow, but eventually abort and ultimately completely fail to regenerate. A look into this mechanism will reveal much about how and why the CNS works the way it does.

Remarkably, almost 90% of cells in the CNS are not even neurons. Rather they are glial cells, which play an important role in supporting neurons both physically and metabolically. They maintain the extracellular environment to best suit and nourish neighboring neurons. The CNS and PNS have two distinct types of glial cells, and they are what accounts for the discrepancy in regenerative ability.

In the PNS, the glial cells are Schwann cells that don't inhibit axon regeneration. Their sole function here is to produce myelin to facilitate more effective transportation of neurotransmitters.

In the CNS, there seem to be two "glial culprits" that inhibit axon regeneration. These are oligodendrocytes and astrocytes. Both play key roles in CNS support and metabolism. It is logical to ask hear, "why on earth would the body ever want to inhibit regenerative ability?" The body has a good answer.

This growth-inhibiting action helps enormously in stabilizing the outrageously complex CNS. This highly organized complex must be maintained, and the growth-inhibitors provide a cellular 'scaffold' so that neurons only sprout to where they are intended. The inhibitors effectively lock the connections into place. Without these proteins, the CNS may not be able to organize itself and work properly. The tradeoff, though, is that the CNS has no ability to regenerate itself in the event of injury. Since the PNS is capable of regeneration, it is evident that cellular mechanisms exist to promote nerve regeneration.

How can nerve damage be fixed?

As of now, there is no cure for nerve damage. To prevent secondary damage, steroids such as methylprednisolone can reduce the swelling that results from spinal cord injury, and Sygen, a recently discovered drug, appears to reduce the loss of nerve function.

However, recent biotechnology holds promise for nerve regeneration. This commercial (requires QuikTime, source: http://www.adcritic.com) by Nuveen Investments shows Christopher Reeve walking, an optimistic and plausible outlook. Explored here are four ways scientists are trying to regenerate nerves in vivo:
1) Guidance Channels
2) Stem Cells
3) Growth Factors
4) Gene Therapy