- My name is Byron Ford.
I'm a professor of Biomedical Sciences
in the UCR School of Medicine.
I'm also Associate Dean for Pre-Clerkship Medical Education
in the School of Medicine.
My research involves Neuregulin Regulation
of Neuroprotection and Neuroinflammation
following Ischemic Stroke.
Blood enters the brain via carotid arteries
in the neck that branch into the cerebral arteries.
These include the anterior cerebral artery in the front,
the middle cerebral artery in the middle
and the posterior cerebral artery in the back.
Stroke occurs when one
of these arteries is blocked or an Ischemic Stroke
while the blood vessel ruptures a Hemorrhagic Stroke.
About 80% of strokes or Ischemic Strokes
and are usually caused
by a clot that blocks the blood vessel.
When the blood vessel is blocked, the brain tissue fed
by that artery dies over the next few hours or days.
You can see in the cartoon that the shaded area
indicates brain cells that are dying
on one side of the brain.
While the other side of the brain is relatively normal.
There is a significant need
for the development of Novel Stroke Treatments.
There are approximately 800,000 strokes
in the US per year, 15 million worldwide.
There's only one drug approved
for stroke Tissue Plasminogen Activator or t-PA
which is a clot Buster drug.
The drug works well however it can only be used
within three hours of the onset
of the stroke and completely as contra-indicated
for hemorrhagic strokes.
It has to be administered in a hospital
with a certified stroke program for safety reasons.
As a consequence only about three to 5% of stroke
patients qualify for t-PA.
Endovascular thrombectomy is an alternative strategy
where the clot is physically removed
by a clot retriever and has a window of six to 24 hours.
In my laboratory.
We model stroke using a surgical procedure
in rats and mice to block the middle cerebral artery.
We insert a filament
with a silicone coated tip into the internal carotid
artery to block the middle cerebral artery.
You can see in this figure
we can measure cerebral blood flow in real time.
And when the filament is inserted to block the MCA
we can see that there's a complete reduction
of cerebral blood flow and when we removed the filament
cerebral blood flow is returned to normal.
You can see histologically
the brain damage occurs after stroke.
In this brat section, red indicates living tissue
and white indicates the tissue that died after stroke.
You can see that there's a large area of damage
on one side of the brain where the other side
of the brain is relatively normal.
We also use a Photothrombotic Cortical
middle cerebral occlusion model in our studies.
In this model a photosensitive compound roast bingo
is injected into the vasculature.
We shine a laser light at 532 nanometers
onto the skull to induce a clot in a selected area.
In this laser speckle image, you can see
that a branch of the middle cerebral artery pseudo colored
red where the blood flow is high.
After stroke in the circle area
you can see that that same blood vessel pseudo
colored yellow blood vessel has been completely
blocked indicating that a stroke has occurred in real time.
For the past 20 years
my laboratory has studied the usefulness
of Neuregulin-1 an indogenous protein to
protect brain cells following stroke.
My lab and others have shown that Neuregulin signals
through ErbB receptors, which work as homodimers
and depending on which dimers are present, can signal
in different ways to facilitate proliferation,
cell survival, growth, and inhibition.
My lab was the first to show that Neuregulin was useful
in protecting brain cells following stroke.
As the previous cartoon showed when
the middle artery is blocked
brain cell damage occurs on one side of the brain
while the other side
of the brain is relatively normal.
Correspondingly, you can see in rat brain tissue
the red indicates surviving cells were white indicates areas
of brain cell damage.
When we treated brain cells
with Neuregulin either before or after the stroke
it resulted in a 90% improvement in neurological function.
In fact, Neuregulin reduces brain damage,
when given up to 13.5 hours
after the stroke and improve neurological function.
There is significant clinical opportunity
for Neuregulin-1 in the treatment of Ischemic Stroke.
Neuregulin would be first
in class as a neuroprotectant to treat stroke.
Neuregulin could also be delivered in an ambulatory
or emergency room setting due to a safety profile.
Neuregulin could also be used
as a prophylactic for cardiac surgery,
for subarachnoid hemorrhage induced vasospasms,
and to prevent post-stroke infection.
Importantly two Neuregulin isoforms are currently
in clinical trial for heart failure.
Neuregulin was shown to be safe
in phase one clinical trials and was shown to
improve cardiac function in phase two clinical trials
of patients with congestive heart failure.
We are currently working
towards developing clinical trials for stroke
in collaboration with Riverside community Hospital.
I would like to thank my current and former lab members
for their assistance with this work and for funding
from the national institutes and other funding agencies.
Thank you.