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CSRO
MAGAZINE BACK ISSUES
In this issue of the CSRO Magazine we are pleased to include one-page
outlines of research projects we are currently funding. We have endeavored
to make the outlines in common terms so everyone can understand the
principles behind the science and most importantly how these studies
are directed towards a cure for paralysis.
How You Can Help Raise Funds
Over the years CSRO has raised funds by hosting events and by being
the designated charity of companies or groups. Every year companies
have events such as golf or hockey tournaments. CSRO has been fortunate
to be named the charity that will receive the proceeds raised. This
is becoming an important source of funding for us. If your company
or a group you know holds an event raising funds please consider
asking them if they would help our cause. We have found that if they
are asked, they usually say they hadn't thought of it and are happy
to help out. Remember, we are a national charity so anyone in Canada
can contribute.
We have three ongoing fundraising programs you can take advantage
of and help us. Speedy Auto Service has generously given CSRO the
opportunity of receiving a portion of whatever the charges are to
us. When you go to Speedy Auto Service for any repair work, simply
tell them you are with CSRO and tell them our AFFINITY number is
0103. They will then contribute to us.
In Ontario Therapy Supplies and Rental has also set up a program
similar to Speedy Auto Service. When you order any supplies or purchase
products from Therapy Supplies, tell them you are a member of CSRO
and they will donate a portion of the payment back to CSRO.
Sunrise Medical has the same program as the above two. Sunrise Medical
sells products across Canada. Again, just mention you want them to
donate a portion of the sale to CSRO and they will be pleased to
do it.
We have implemented a new program called Planned Giving. It is a
simple, convenient and effective way to help fund valuable research
here at CSRO. It gives you the personal satisfaction of knowing that
your gift will make a difference to the lives of many people in the
future.
In addition to helping CSRO our Planned Giving program offers other
benefits to you the donor. It allows you to take advantage of the
tax incentives associated with such programs.
Planned giving is a gift that is arranged now and provides funds
or assets to CSRO now or in the future. It is a gift, bequest or
transfer made through an estate or financial plan. This can be done
through will bequests, life insurance policies or charitable annuities.
If this type of giving is of interest to you, please contact us here
and we will send out our Planned Giving booklet to you.
As you can see, there are ways you can contribute to CSRO very easily.
We are very proud of our research program and with your help we will
get to our goal of a cure for paralysis. So pitch in! You will feel
proud you did!
Sincerely,
Ray Wickson
President, CSRO
| Cranex
as an Agent in the Treatment of Urinary Tract
Infections |
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to Top |
One of the greatest problems facing individuals with a spinal cord
injury is bladder infections. They are caused mainly by E. coli bacteria,
which are normally found in the intestinal tract but manage to make
their way into the sterile environment of the urinary tract. The
bacteria are able to cling to the wall of the bladder and multiply,
thereby causing a bladder infection. Currently, antibiotics are being
used to treat this condition, which creates a risk of developing
bacteria that are resistant to treatment.
A possible alternative to antibiotics is CRANEX. One of the main
ingredients is cranberry extract which serves two purposes. First,
it contains a chemical called hippuric acid which makes the urine
more acidic, creating an unfavorable growth environment for bacteria
to flourish. It also contains large amounts of specific compounds,
called condensed tannins or proanthocyanidins, which prevent E. coli
from attaching to the cell wall of the urinary tract, a major step
in the infection process. It does this by inhibiting the growth of
the receptors on the end of the arm-like appendages, called pili,
that allows the bacteria to bind to the cell wall. This causes them
to become slippery, which makes it easy to flush the bacteria out
of the system and avoid infection.
The anti-adherance activity found with CRANEX allows it to be used
as a substitute for antibiotics. Treatment involves the administration
of CRANEX capsules four times daily. Human clinical trials are currently
in the works to determine the effectiveness of this type of treatment
in the reduction of urinary tract infections.
By: Anita Shama, Canadian Spinal Research Organization
The spinal cord makes up part of the central nervous system (CNS).
After an injury, damaged nerves in the CNS are unable to repair themselves
due to an unfavorable growth environment. The CNS lacks molecules
called neurotrophic factors (NTFs), as well as guidance channels
and substrates that aid in nerve repair. In addition, the injury
induces the release of myelin growth inhibitors, axon degeneration,
chronic inflammation, and formation of scar tissue which impedes
nerve regrowth. Gene therapy is a method currently being tested to
determine whether nerves can regrow across an injured area.
Cells are removed from the rat. There are two types being used that
are available in limitless numbers:
FIBROBLASTS - are skin cells that naturally secrete substrates required
for nerve growth
SCHWANN CELLS - are found in the peripheral nervous system. They
myelinate peripheral nerves to speed up signal transmission and aid
in nerve regeneration by naturally secreting NTFs and substrates.
NTFs are proteins that can regulate neuron survival and axon growth.
There are more than 40 different CNS growth factors. Example: NT-3
(neurotrophin-3)
The NTFs are incorporated into viruses which in turn infect the rat
cells.
The infected cells have been genetically modified to contain the
gene with the neurotrophin which causes them to grow and secrete
the NTFs.
Grafts are created containing numerous fibroblasts or schwann cells.
They provide NTFs and substrates that promote nerve growth and survival,
as well as an environment free of growth inhibitors. The substrate
molecules collagen, fibronectin, and laminin provide a location for
the nerves to attach and extend.
The graft containing the cells are transplanted back into the same
rat. This prevents graft rejection since the rats own cells are used.
An advantage to this method is that the NTFs are produced and secreted
directly into the area of injury.
The same rat that originally had the cells removed would undergo
surgery to transect the spinal cord leaving a gap.
The grafted cells cause regeneration of motor and sensory neurons.
However, different axons have different preferences for various growth
substrates and NTFs.
By: Anita Shama, Canadian Spinal Research Organization
| Intravesical
Capsaicin For Treatment of Neurogenic Bladder |
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to Top |
The main control center for bladder function is the brain. It enables
voiding to take place at low pressure by causing the detrusor muscle
in the bladder to contract and the sphincter muscle to relax. There
are also nerves which extend from the sacral part of the spinal cord
that activate the detrusor muscle. These sensory nerves send information
from the bladder to the spinal cord telling it when the bladder is
full or in pain.
After a SCI the bladder is no longer controlled by the brain. The
sacral nerves cause the bladder to become spastic, also known as
detrusor hyperreflexia, at low volumes of urine. Since the sphincter
muscle is no longer able to relax, the bladder pressure increases
leading to renal failure and eventually death if left untreated.
CAPSAICIN is a neurotoxin found in hot peppers. It has the ability
to block sensory nerves involved in bladder spasticity. It does this
by binding to receptor sites on the nerve fibres. This leads to depolarization
of the nerve causing them to release neuropeptides from their terminals.
Initially, the nerves are excited but the neuropeptides are quickly
depleted and the nerves are desensitized.
The effect is long term since blockage of the main transport of the
neurotrophic factor causes a reduction in neuropeptide production.
For persons experiencing hyperreflexia, this causes an increase in
their bladder capacity and lowers the pressure in their bladder making
them less prone to kidney damage.
The objective of the study is:
- To reduce the detrusor leak point pressure (DLPP), which is
the bladder urine storage pressure tobelow 40 cm H20.
- To increase the bladder capacity to above 250 ml.
- To decrease the urgency of urination, detrusor hyperreflexia,
and autonomic dysreflexia.
To reduce or eliminate incontinence.
Capsaicin is injected into the bladder through a catheter and held
for 1 hour. The dosage varies between patients depending on their
degree of bladder control. Side effects may include autonomic dysreflexia
or supra pubic pain for a few minutes during time of injection.
The future aim is to eventually be able to predict the dosage of
capsaicin, ditropan, and IC required to control the bladder pressure.
By: Anita Shama, Canadian Spinal Research Organization
THERE ARE TWO MAIN SITES OF NEUROLOGICAL DAMAGE THAT OCCUR AFTER
A SPINAL CORD INJURY:
- AXONS - long nerve cell processes that run up and down the
spinal cord carrying motor and sensory information between nerve
cells.
- NEURONS - nerve cells that carry and process information over
short distances in the spinal cord.
These processes have the potential to regenerate but don't normally
do so because inhibitors in the spinal cord present an inhospitable
growth environment. One way of attempting to overcome neurological
damage is by transplanting neurons from the intestine to the injury
site. The intestinal nervous system is similar to the CNS. Enteric
neurons are able to express a wide range of neurotransmitters, available
in abundance, and do not cause host rejection since they are grafted
back into the same individual. The transplanted nerve cells might
connect with damaged cells to form connections across the region
of injury, or they may directly replace cells lost through injury.
Another approach is the transplantation of enteric glia at the site
of injury. These cells are similar to CNS astrocytes. They are supporting
cells in the nervous system that function to ensheath axons and provide
trophic factors which stimulate the growth and survival of neurons
to extend and contact other nerve cells. After transplantation, the
glia migrate up and down the spinal cord making paths for regenerating
nerve cell processes to follow. The glia also help in preventing
further tissue degeneration at the injury site.
The ability of the glia to release trophic factors is triggered by
messages sent from chemicals called PURINES. They make up part of
the basic components of DNA and RNA. After an injury, all cells release
large quantities of purines which help to protect from further damage
to other neurons. The purines also cause the glia to release trophic
factors to aid in repair. Often, the purine levels are insufficient
in producing any significant changes so a synthetic purine has been
created to supplement those naturally occurring. Currently, the effectiveness
of the synthetic purine and its mechanism of action are being determined.
By: Anita Shama, Canadian Spinal Research Organization
| The
role of purines in the repair of damaged nerves |
Back
to Top |
After a spinal cord injury, damaged cells release large quantities
of chemicals called purines. Purines makeup part of the basic components
of the genetic material (ex. DNA), as well as acting as the energy
currency of cells. There are two types of purines, adenosine and
guanosine, which also play important roles outside cells. They signal
nerve cells to protect themselves from further damage, and also act
as chemical messengers to signal cells called astrocytes and glia
to release trophic factors. Glia and astrocytes are supporting cells
in the CNS, and the trophic factors that they secrete aid in the
repair of damaged nerves. Unfortunately, the purines released from
injured cells do not accumulate to large enough amounts to have significant
effects. Thus, a synthetic purine has been created to supplement
those naturally occurring. This synthetic purine, also known as AIT-082,
is a derivative of guanosine. AIT-082 is active when orally ingested,
so there may be a potential drug use.
In addition to the effects already mentioned, guanosine and AIT-082
also stimulate the release of adenosine by astrocytes. Thus, adenosine
release occurs from both the initial damaged cells, as well as being
induced by guanosine and its derivative. The only problem is that
the release of large quantities of adenosine by injured or dying
cells seems to reach local concentrations high enough to signal apoptosis,
a genetically programmed cell death. This process occurs via a receptor
on the cell surface of the astrocytes, called the A3 receptor. Apoptosis
of the astrocytes results in the loss of the neurons they support.
Blocking the A3 receptor could prevent the inappropriate signaling
of apoptosis by adenosine, yet allow the positive circulatory and
trophic effects signaled through two other adenosine receptors.
Treatment of SCI rats with AIT-082 resulted in less swelling and
necrosis (cell death resulting from trauma) of their spine. A downside
to the usage of AIT-082 is that it negatively interacts with a drug
called methylprednisolone, which is initially administered in high
amounts in spinal cord injuries. The preliminary tests are being
conducted to determine the methods of administration that will maximize
the potential use of these two drugs in the future.
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