Could Frankenstein be a reality?

Nearly two centuries ago, constructing a human life was merely a thought of
imagination. The legendary novel Frankenstein by Mary Shelley was the novel that
introduced this idea to the world. Mary Shelley says it best “Life and death appeared to
me ideal bounds, which I should first break through, and pour a torrent of light into our
dark world.” The idea that one could fathom such an idea that early in human history is
an utter state of consternation. Weaving the nerves that control our senses and even
our mental states of emotion to reconnect our control center, the brain, to the rest of our
body, is much like a spell of magic. There is much science to be overcome but there is
magic that takes place too. Recreating a personʼs spine, thus reconnecting the brain
back to the body, is an idea of the past and the reality of our future.
Dr. John D. Houle of Drexel University in Philadelphia, Pennsylvania, is on the
cutting edge of spinal regeneration in animals. The research at hand is of utmost
importance because it will readily be applied to us when such a discovery allows the
leap from animal to human. Dr. Houle began his spinal regeneration research interest
at Purdue Universtiy while receiving his PhD. He then moved on to the University of
Florida and the University of Saskatchewan to complete his post-doctoral fellowship.
His time spent at these institutions, lead him to become a faculty member for the
Department of Neurobiology and Developmental
Sciences at Arkansas University.
These experiences has given him the basis for his
research at Drexel University, where he resides as a
Professor within the Department of Neurobiology and
Anatomy. His focus has remained on correcting
spinal lesions (injury) in mice for many years. He is
funded by the National Institute of Neurological
Disorders and Stroke (NINDS). When a spine has a
lesion, the signals from the brain to the body are
relayed a bit slower or possibly not at all. It is
somewhat similar to that of a short in an electrical circuit. Dr. Houle set out to solve this
dilemma, and has had his fair share of successʼ.
The Central Nervous System, most commonly shorthanded CNS, is the control
center of our bodies sensesʼ, emotion and mental states. It consists of the brain, the
spinal cord and the retina of the eye. It accomplishes such a task by relaying these
signals to our brain, which consists of biological switches and electrical impulses that
are turned on or off to establish the appropriate response for our body. These signals in
question are much like on a race track, they are happening extremely fast but are going
around a closed circuit, known as a neural circuit. The “action potential” jumps from
neuron to neuron (explained below) by channels that open due to chemical
concentration around the cell. The cell has a voltage, an electrical state if you will. It is
extremely small, but the ratio of change is what generates such action potentialʼs, these
electrical signals that are ever so important.
 A spine consists of
many components as
shown in this picture
below. The gray matter
is in the center of the
cord, in the shape of an
“H.” Gray matter is
crucial to the
development of new
nerve tissues and
axons. Axons are the
part of the neuron that
transmit the electrical
impulses from the
dendrites to the axon
terminal. Without
axons transmitting the
signals, there would not
be a connection.
These neurons are
“connected” by
Image Link:
http://www.csuchico.edu/~pmccaffrey/syllabi/CMSD%20320/images/U8CrossSec.jpg

synapses, which is a small gap between cells. An electrical impulse is relayed to

another axon through chemicals being passed through this small synapse as seen in
the picture below. Within this experiment the vertical PNG that is created travels from a
C3 lesion site to the C5 dorsal quadrant and the grafted nerve must be able to connect
grey matter tissues in order for
the neural circuit to work
correctly. Connecting the grey
matter can be thought of
reinstating the neural
connection and thus
reestablishing the axons
activity. The chemical impulse,
action potential, travels from
the dendrites or cell body to the
axon terminal and then
commences the process in the
synapse.

Image Link:
http://www.benet.org/teachers/
meraci/Neuron_Synapse.jpg
The figure below represents the spine vertically to show where the locations of C3 and
C5. C3 and C5 are the nerves that are connected by the PNG.
In order to do this, Dr. Houle designed
an idea that would basically create
another route for the “signal” to be
transfered from the brain to the body. In
other words, he went around the lesion
site and outside the spinal cord. A
rather involved experiment of his
consisted of inducing spinal lesions to
lab mice, and then testing this “round
about” method on them. The mice were
tested for their function after the
procedure by certain physical and
mental challenges. To begin, an
enzyme by the name of Chondroitinase
ABC (ChABC) was used to cleave side
chains of glycosaminoglycans (GAGs).
GAGs are molecules that are known to
inhibit the growth of axons. GAG is any
group of molecules that are components
of connective tissue. They consist of
polypeptides with amino groups
attached. In addition they are a
member of the chondroitin sulfate
proteglycan (CSPG) family. A
proteoglycan is a compound that
contains a protein attached to a
glycosaminoglycan. These proteglycans
are known to be notorious for their
repulsive features towards scar-
associated ExtraCellular Matrix (ECM)
molecules, meaning a scar will not likely
form as they do for the majority of the
time. What Dr. Houle set out to do was
to skip the lesion site by regeneration of
axons using a Peripheral Nerve Graft
(PNG) from the mouseʼs tibia. In order
to stimulate re-growth from the lesion
sites, ChABC was administered in
Image Link: http://www.frca.co.uk/images/spinal-cord.gif
measured doses to the ends where the lesion sites were.
 This figure to the left, is a result from an
immunocytochemical test for CSPGʼs. This
basically means that cells with their ECM
disrupted are tagged and each column is a
different treatment, saline vs. chondroitinase.
Take notice that the section in question is
outlined. The ChABC column has a more dense
representation of CSPGs than the saline
treatments. This is of importance because this
means that the ChABC has produced more
CSPGs, which means that there is more axon
growth near the lesion
site.
Both Image Links: http://
www.jneurosci.org/cgi/content/short/
26/28/7405

In this figure to the right, the upper left

illustration is a visual of exactly what
the PNG is doing and what it looks like
within the spine. The space the PNG is
passing through is known as the grey
matter as shown in the previous figure.
This allows the lesion site to be passed
over and the signal “circuit” to be
completed, thus allowing function to be
reinstated.
The results were interpreted by using
immunocytochemical staining after the
PNG had begun to grow. The stains
were used to tag re-growth in axonal
and the spinal nerve cells. For a spinal
cord to fully function, the peripheral
nerve (mouse tibia nerve) must be able to grow into the “H” of the spinal cord, where the
neural cell bodies reside. The “grey matter”, the H of the spinal cord, is responsible for
routing the signals for the Central Nervous System (CNS). The PNG is the nerve cells
growing from one axonal lesion site, C3Hx lesion, outside of the spinal cord and into the
grey matter of the spinal cord tissue at C5. The PNG must do two things: first grow
around the lesion site and connect both lesion ends; second, the PNG must grow into
both ends of the lesion site connecting with axonal cells, thus completing the “circuit”;
and third, this graft must obtain normal function for the mouse, movement, behavior, etc.
This brings us to the last testing stage within this experiment, the movement and
behavior of the mice after the PNG had been completed. The tests done were just
basic exercises, such as walking across a rope, or the cylinder test. However, since in
this situation the tibial nerve was used as the graft nerve (PNG) then the right hindlimb
 of all subject mice were hindered.
None the less, each test was
conducted with this in mind, and
done unbiasedly. Examples of
these tests include a rope walk
and a wheel walk, as seen in the
figure to the left. As the figure
shows, some mice have lost the
front right limbsʼ function due to
the improper treatment. This
experiment contained much
detail, science and phenomena
that have yet to be explained.
Image Link: http://neuro.cjb.net/
cgi/content/full/26/28/7405

Dr. Houle has found many useful techniques and many are still being discovered.
He continues to do his research at Drexel University to this day, and will continue to
uncover more possibilities to hopefully one day solve the problem of spinal regeneration
in spinal injury. Philadelphia, Pennsylvania has hosted this world renowned research
and is honored to have such an accomplished individual so close to home.

References:

1. Houle JD, Tom VJ, Mayes D, Wagoner G, Phillips N, and Silver J.(2006) “Combining
an Autologous Peripheral Nervous System “Bridge” and Matrix Modification by
Chondroitinase Allows Robust, Functional Regeneration beyond a Hemisection Lesion
of the Adult Rat Spinal Cord.” The Journal of Neuroscience. http://www.jneurosci.org/
cgi/content/short/26/28/7405

2. Houle JD, Ziegler MK.(1994) “Bridging a complete transaction lesion of adult rat
spinal cord with growth factor-treated nitrocellulose implants.” Journal of Neural
Transplant Plast. Pp.115-124. http://www.ncbi.nlm.nih.gov/sites/entrez?
Db=pubmed&DbFrom=pmc&Cmd=Link&LinkName=pmc_pubmed&LinkReadableName
=PubMed&IdsFromResult=2565283&ordinalpos=5

3. Shelley, Mary. Frankenstein. Published in France. 1818.

4. Picture of John D. Houle, PhD. http://neurobio.drexel.edu/houleweb/houle.html

5. Department of Neurobiology and Anatomy, Drexel University. John D. Houle.

“Neurotransplantation Strategies to Promote Structural and Functional Recovery after
Spinal Cord Injury.” 2005.

6. Drexel University image. Philadelphia, PA.

 http://www.drexel.edu/images-core/at-a-glance-enlarge.jpg

7. National Institute of Neurological Disorders and Stroke. “Spinal Cord Injury:

Emerging Concepts.” 22 June, 2007. http://www.ninds.nih.gov/news_and_events/
proceedings/sci_report.htm#Anatomical

8. The Dana Foundation. “Spinal Cord Injury-Harnessing Regeneration and Immune

Defenses.” Brenda Patoine. http://www.dana.org/news/publications/detail.aspx?
id=4272

9. “Spinal Cord Injury Research.” Mayo Clinic. http://discoverysedge.mayo.edu/

spinal_cord_injury/index.cfm

10. Monaghan JR, Walker JA, Page RB, Srikrishna P, Beachy CK, Voss SR. “Early
gene expression during natural spinal cord regeneration in the salamander.” The
Journal of Neurochemistry, pp. 27-40. 2007.