Tyler Sweeney

Dr. Alan Jalowitz

201B Patee Library
Penn State Universtiy
University Park, 16802

Proposal to the Editor

Dear Dr. Jalowitz,

-Why spinal cord regeneration?

All vertebraes have a spine that relays the signals of the brain to the rest of our body. If
any section of the spine were to become injured, this has the potential to cause
paralysis or brain damage. Spinal cord regeneration in animals is a field that has
become quite developed in the past few decades. The first idea of regeneration was
recorded in the novel, Frankenstein by Mary Shelley. This imaginable idea was
unobtainable until now. Many researchers have discovered many revolutionary
techniques to regenerate neurons and provide a bridge over lesions in the spinal cords
of animals. Spinal cord injuries are very grave because it effects the the Central
Nervous System (CNS). The CNS controls everything from emotion to reflexes to pain.
The reason this topic interests me the most is because this field is headed into the
unknown. Exploration is your best tool in this situation, and your intuition is your only
instinct. Any thought is considered a possible solution to this issue. This topic opens
the mind to possibilities that are unseen by anyone. In addition, this topic appeals to
myself because it has the potential to help many of people. If some way, a technique
came about to heal, or regenerate spinal injuries, then endless possibilities could be
presented and used to help people around the world.

-Why me?

I believe I am qualified to write on this subject because foremost I am a double major in

Immunology and Infectious Disease, and Toxicology. These majors provide the ample
medical and scientific based background that allows me to understand the research at
hand. I am and have been doing research with various subjects in a research lab here
on campus. Being in this atmosphere allows for my thought process to be in tune with
that of a researcher. It easier for me to relate to this subject than others, and I can
explain and write it in such a way that others may understand this the way I do. The
language used within these research articles is hard for many to understand but with my
help it can be made simpler.
 Tyler Sweeney

-What was researched?

The research that I conducted for this topic was rather limited due to the fact that this
topic is world renowned and this article represents the research done in Pennsylvania at
Drexel University. I found most of the articles for John D. Houle as him being the first
author. This means that he was the primary investigator by himself or with another
collaborating investigator. I did find some sources that I will be using to represent the
importance and the concepts that this topic entail. Many sources are researched based
which means the concepts are experimental and may be disputed in other researchers
opinions. The research papers I found were accredited and backed up by other
concepts and researchers that were working on the same topic.

-The technicalities

Dr. Houle has been researching spinal regeneration in animals for more than a decade.
He has discovered useful techniques in this field, and the technical aspects of his
scientific discoveries are presented here in a simple manner. His research consists of
trying to reinstate spinal cord function across a lesion site. To go about this, he used
rats and he induced lesion sites in a set population of them. The easiest way to explain
this research is to give an overview, so that one can understand the big picture. Dr.
Houle used an enzyme known as Chrondroitinase ABC (ChABC). This enzyme has
previously been researched by many, and they have found that it cleaves the side
chains of glycosaminoglycan (GAG). 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 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 mouses
tibia. In order to stimulate re-growth from the lesion sites, ChABC was administered in
measured doses to the ends where the lesion sites were. The results were
interpreted by using immunocytochemical staining after the PNG had begun to grow.
The stains were used to tag axonal re-growth and the spinal nerve cells. For a spinal
cord to fully function, the nerve cells and the axon cells must come in contact, hence the
point of this experiment. The PNG is the nerve cells growing from one axonal lesion
site out into the gray matter of the spinal cord tissue, outside the axonal cell tissue, and
is then connected to the to the other lesion site. 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
 Tyler Sweeney

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. This experiment contained much detail, science and
phenomena that have yet to be explained. I hope I have simplified it enough to the
point that one can understand the use of such a technique.

-Conclusion

Dr. Jalowitz, I formally ask for your permission to write this article in hopes of it being
published to your liking. I believe that I have provided you with ample reasons of why I
am qualified to write on this subject. My sources are of the highest quality, due to the
fact they are first hand written accounts from the research labs. This topic may present
many difficulties, but I am confident that I can solve these issues and lay the concepts
out in an easy to understand format. I would be honored if you would allow me the
privilege of writing this article. Thank you for you time and I hope we will be
collaborating about this article sometime in the near future.

Sincerely,

Tyler Sweeney

Images:
 Tyler Sweeney
 Tyler Sweeney

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

-Excellent quality
-Describes the science behind his discoveries
-This will allow for me to explain the science

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
- excellent
- Dr. Houle wrote this article, its about his approach to gapping the spinal lesion
- helps myself understand the overall reason for this process and others

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

-Good source
-First written account of regeneration, a thought at least
-Gives the reader a common ground for understanding

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

-Excellent
-Gives image of John D. Houle
-Helps reader visualize him

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

Neurotransplantation Strategies to Promote Structural and Functional Recovery after
Spinal Cord Injury. 2005.
-Excellent
-Gives overview of his research interests
-Will make the material easier to read

6. Drexel University image. Philadelphia, PA.

http://www.drexel.edu/images-core/at-a-glance-enlarge.jpg
good source
 Tyler Sweeney

gives visual of Drexel University

shows reader place of research

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
solid reference
gives overview of research and discoveries within the field
helps me to relay the big picture to the reader

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

Defenses. Brenda Patoine. http://www.dana.org/news/publications/detail.aspx?
id=4272
excellent
very good overview of the subject matter from different party
helps me further explain the research at hand

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

spinal_cord_injury/index.cfm
awesome source
gives other research results, different viewpoints
further explains the research field from other researchers

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.

great source
a research paper that provides different edge on the topic
hopefully will provide another outlook on research