The Toronto Hospital Neurosciences Research Program
( Toronto, September 4, 1996) The Toronto Hospital Neurosciences Research
Program is the largest in Canada and one of the largest in North America.
The research arm of the Program is called the Playfair Neuroscience Unit.
It was established in 1978 and comprises more than 40 principal investigators.
The investigators include basic scientists, clinician scientists, physiologists,
pharmacologists and molecular biologists. Research in the Playfair Neurosciences
Unit is focused on the nervous system, neurodegenerative disease and nerve
injury. As well, research is conducted on Alzheimer's disease, Parkinson's
disease, epilepsy, spinal cord and brain injuries, brain tumours, sleep
disorders, vision and hearing disorders and drug addiction. Below is a brief
description of some of the current research:
1) Functional MRI, Dr. David Mikulis and others. Functional Magnetic Research
Imaging is a state-of-the-art method for imaging brain activity. It measures
changes in blood flow produced by groups of nerve cells in the brain that
carry out specific actions including movement, speech, memory and cognition.
Functional MRI is used in epilepsy, stroke, pain, Parkinson's disease and
spinal cord injury research.
2) Parkinson's disease Research, Dr. Anthony Lang, Dr. Andres Lozano and
others. Deep brain stimulation is an investigational treatment for Parkinson's
disease, a chronic, slowly progressive disease of the nervous system. During
this procedure microelectrodes are placed in the globus pallidus, the part
of the brain that controls movement. These electrodes or wires are connected
to a stimulator placed just below the collarbone. The stimulator, much like
a heart pacemaker, regulates the diseased brain cells to stop them from
sending the abnormal electrical signals which cause the movement disorders.
Patients control their symptoms by activating a stimulator.
A growth factor treatment for Parkinson's disease is also being investigated
at the Hospital. The growth factor is known as Glial Derived Neurotrophic
Factor (GDNF). This growth factor has very pronounced effects on dopamine
neurons. GDNF has been shown to protect dopamine neurons from toxin damage
caused by various types of injury in animal models of Parkinson's disease.
3) Spinal Cord Injury Research . Dr. Michael Fehlings' Laboratory. This
laboratory is using cellular and molecular techniques to find a cure for
paralysis after central nervous system (CNS) injuries such as spinal cord
injury, brain injury and stroke. The researchers in this lab are focusing
on two main strategies:
a) reducing entry of sodium and calcium into injured cells to reduce "secondary
injury." The lab has recently cloned the gene for an enzyme called
"calpain" which is activated by calcium and causes destruction
of nervous tissue after spinal cord injury, brain injury or stroke. The
lab is examining drug and gene-based therapies to prevent sodium and calcium
associated cell damage.
b) The researchers are also interested in maximizing functional recovery
after spinal cord injury. This group is using molecular genetic strategies
to target a family of potassium channel on nerve fibres to improve signal
transmission after spinal cord injury. The aim of this work is to improve
neurological function of individuals with paralysis due to spinal cord injury
of other CNS disorder. Dr. Tator's laboratory (Axonal Regeneration). This
lab is studying the ability of the nerve fibres (axons) to regenerate. A
model of spinal cord injury was created in a dish so that we could examine
the exact factors involved in regeneration. The researchers in this lab
found that nerve growth factor was an essential ingredient for regeneration.
Within 36 hours of an acute transection injury which simulates human injury,
the axons were able to grow across the dish. This experiment was performed
with superior cervical ganglion cells from the rat, and the next step is
to attempt to repeat this experiment with spinal cord neurons.
In summary, this lab has created an excellent model for studying spinal
cord injury in a dish (in vitro) and has identified some of the essential
factors for regeneration.
4) Epilepsy Research, Dr. Peter Carlen and others. A newly established priority
at the Hospital is the Epilepsy Program. It comprises major efforts in clinical
care and both fundamental and clinical research. The areas of research in
basic science include: how brain cells communicate to each other in epilepsy
· how brain cells are altered in epilepsy · new drug strategies
in epilepsy treatment · gene identification in epilepsy · how
to protect brain cells during seizures Clinical research in epilepsy includes:
· clinical trials of new anticonvulsant drugs (Ramecamide, Tiagabine,
Lamotrigine, Topiramate, Gabepentin) · women and epilepsy (seizure
incidence related to menstrual cycle) · MRI in epilepsy; functional
MRI, MRI spectroscopy · migraine in epilepsy · EEG (brain wave
activity) in epilepsy
5) Cellular Neuroimmunology Lab, Dr. Lyanne C. Schlichter The Central Nervous
System (CNS) is comprised of three major classes of cells: neurons, astrocytes
("glia") and microglia. Microglia behave as the resident immune
cell in the CNS. Like immune cells in the rest of the body, they protect
against infections, but can cause damage if they are over activated or attack
their own cells. It is only in the past several years that microglia are
coming under intense study. They now seem to be involved in almost every
disease or damage to the CNS, including stroke, trauma, spinal cord injury,
Alzheimer's and Parkinson's disease and AIDS dementia complex. It is clear
that treatments of CNS disorders cannot ignore immune cells and focus only
on the neurons. This lab, and a number of labs throughout the world, focuses
on microglia function. The goal is to find ways to regulate these cells
to help promote recovery from a wide range of insults to the CNS.
6) Stroke Research, Dr. Chrisopher Wallace and others. Stroke causes the
death of brain cells when vital blood flow to them is obstructed. If flow
is not restored within minutes, brain function can be permanently lost.
It's known that these cells die because of an alteration in the amount of
calcium that flows into them. At the Playfair Neuroscience Unit, a novel
protection strategy has been developed and patented. A special calcium chelator
introduced into the cells before the stroke results in an increased resistance
to dying. This strategy will be employed in patients in the early stages
of a stroke, or those undergoing risky neurosurgical or cardiac bypass procedure.
The health and cost benefits to patients with stroke will be enormous.
7) Brain Functioning Research, Dr. Nancy E. Noldy. Brain injury, neurological
disorders and drugs that affect the brain often cause changes in cognitive
functions such as memory and attention. Some of these changes in brain functioning
can be examined by recording electrical brain activity from the scalp while
a cognitive task is performed. Dr. Nancy E. Noldy is using this technique
to examine the effects of seizures on information processing in people with
epilepsy and to research sex differences in brain functioning which may
lead to different consequences for men and women when injury occurs.
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