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Research Programs

Stroke

Stanford 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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NEUROSURGICAL LABORATORIES
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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Clinical Trials
Current clinical trials include new stroke prevention and treatment studies:

  • 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.