Stroke Center brings together physicians from multiple specialties,
including neurology, neurosurgery, neuroradiology, internal medicine
and emergency medicine to provide comprehensive evaluation and management
of patients with cerebrovascular diseases. Treatments include medical
therapies, advanced surgical techniques, and neuroradiology procedures.
The Center is at the forefront of new developments in drug therapy
for the emergency treatment of stroke and stroke prevention. These
emerging therapies are available to patients in clinical trials
directed through the Stroke Center.
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Under the direction of Pak H. Chan, Ph.D., Director of Research
for the Department of Neurosurgery, research investigations conducted
in the Neurosurgical Laboratories elucidate the cellular and molecular
mechanisms of cell death and regeneration in brain after stroke,
trauma and neurodegenerative diseases. The lab develops therapeutic
strategies to reduce brain injury in preclinical settings.
Researchers in the Neurosurgical Laboratory include collaboration
between Dr. Pak Chan, Dr. Midori Yenari, and Dr. Gary Steinberg
from Neurosurgery, Dr. Rona Giffard of Anesthesia, and Dr. Robert
Sapolsky of Biological Sciences. Their work is supported by several
NIH R01 and Program Project grants.
Dr. Chan, a Jacob Javits Neuroscience Investigator Awardee,
has employed transgenic mice and rats to elucidate the oxidative
mechanisms of stroke pathogenesis and neuronal apoptosis. His work
has demonstrated that oxygen radicals, mitochondrial cytochrome
c, and the caspase family of proteins participate in ischemic cell
death. These novel studies provide an impetus for future development
of therapeutic agents in treating brain injuries after ischemia,
trauma and neurodegenerative diseases.
Dr. Steinberg's research interests focus on the area of
neuroprotection for cerebral ischemia. Gene therapy and cell transplantation
are two new potential areas of stroke treatment. Using viral vectors,
it is possible to improve neuron survival by transfecting them with
genes involved in improving metabolic substrate (glucose transporter),
buffering intracellular calcium rises (calbindin), preventing protein
aggregation or protein malfolding (HSP72), anti-apoptotic proteins
(Bcl-2) and antioxidant genes (glutathione peroxidase). Current
work, funded by the National Institutes of Health (NIH), now focuses
on the precise mechanisms underlying the observed protection, and
whether such gene therapy can be given after stroke onset, or in
related brain injury. Studies of stem cell transplantation are underway
to determine whether they might also protect the brain from ischemia,
and whether new cells are generated in the brain after stroke (neurogenesis).
A second area of research involves understanding why hypothermia
protects the brain from stroke. Recent work has shown that mild
hypothermia is associated with decreased oxidative stress and also
prevents the brain from expressing many damaging proteins. These
projects involve collaborations with Stanford neurobiologist Dr.
Robert Sapolsky (Biological Sciences), neuroscientist & anesthesiologist
Dr. Rona Giffard (Anesthesiology), stem cell biologist Dr. Theo
Palmer (Neurosurgery), and animal behaviorist Dr. Timothy Schallert.
Dr. Yenari's research interests lie is the area of inflammatory
responses in the brain following cerebral ischemia. She is currently
funded by the National Institutes of Health (NIH) and the American
Heart Association to study the contributions of peripheral leukocytes
and microglia to secondary ischemic injury. Her lab studies stroke
and brain inflammation models to better understand how white blood
cells and microglia (the "white blood cells" of the brain)
are involved in ischemic injury. Her lab also studies neuroprotective
strategies such as hypothermia, pharmacological inhibitors of leukoctye/microglial
activation and gene therapy of specific potentially neuroprotective
genes to modulate this response. Another research interest of Dr.
Yenari is that of gene expression following stroke. Work in her
lab demonstrated that overexpression of some potentially neuroprotective
genes or inhibition of potentially damaging genes improves stroke
outcome. These projects involve collaborations with Dr. Rona Giffard
(Anesthesiology), Dr. Raymond Sobel (Pathology), Dr. Robert Sapolsky
(Biological Sciences), Dr. Daria Mochly-Rosen (Molecular Pharmacology),
and Dr. Francis Blankenberg (Radiology).
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Current clinical trials include new stroke prevention and treatment
- A study which will determine whether neuroimaging with MRI (DWI)
can help identify patients that can benefit from thrombolytic
therapy with rt-PA beyond the 3 hour treatment window.
- Patients with acute stroke (<48 hours) are evaluated with
diffusion weighted MRI (DWI) and perfusion MRI. These new, non-invasive
techniques are very sensitive at detecting acute brain injury
and may be very helpful in guiding stroke evaluation and management.