By Wayne Gillam / UW ECE News
In a first-of-its-kind demonstration, UW ECE and BioE Associate Professor Azadeh Yazdan and her research team have shown that applying electrical stimulation to the brain within an hour after the onset of an ischemic stroke may significantly reduce brain damage. This work is an important step forward for stroke intervention research, and it points toward a new way of treating stroke soon after it occurs. Shown above: Yazdan examines a 50-micron-thick brain section, which is stained to highlight important structural features of brain cells. Photo by Mark Stone / University of Washington
Azadeh Yazdan has a clear vision for her neural engineering research — to translate this work into clinical applications that can make a positive and even profound difference in people’s lives. And Yazdan, who is the Washington Foundation Innovation Associate Professor of Neuroengineering in UW ECE and the UW Department of Bioengineering, is well on the way to making her vision a reality. As a neural engineer, she tackles some of the most devastating and difficult-to-treat diseases and afflictions people can face, such as Alzheimer’s disease, mental health disorders, and stroke. These health conditions affect the lives of millions of people around the world.
For example, take just one condition Yazdan is investigating, ischemic stroke. Globally, over 7.6 million people suffer an ischemic stroke each year, causing significant health, economic, and lifestyle impacts to those that undergo the stroke as well as to their loved ones. An ischemic stroke is common, making up well over 70% of the strokes that occur. It happens when a blood vessel to the brain becomes blocked, cutting off blood flow and leading to brain cell death.
Neural engineers have been working for several years now toward using electrical brain stimulation to treat stroke, encouraged by successes in other areas, such as deep brain stimulation for Parkinson’s disease. It is well-known that prompt treatment for strokes is crucial to obtaining better outcomes. However, most medical researchers and health practitioners have shied away from attempting to use electrical stimulation to treat a stroke soon after it occurs, when it is considered an “acute” stroke, for fear of causing further damage to the brain.
But now, in a first-of-its-kind demonstration recently described in the journal Nature Communications, Yazdan and her research team have shown that applying electrical stimulation to the brain within an hour after the onset of an ischemic stroke may significantly reduce brain damage. This work is an important step forward for stroke intervention research, and it points toward a new way of treating stroke soon after it occurs.
“The number of people that this treatment could impact is really high, and I think that out of all the research I’ve done so far, this work is the closest to translation.” — UW ECE and BioE Associate Professor Azadeh Yazdan
“This finding was something that was very surprising and unexpected, not only for us, but for the field,” Yazdan said. “In the acute phase after a stroke, the brain is highly sensitive due to network damage and imbalance, which significantly increases the risk of seizures. Consequently, electrical brain stimulation is typically avoided during this period. However, our findings suggest that targeted stimulation can have a neuroprotective effect and may even help prevent seizures or other pathological neural events that contribute to further brain injury.”
UW BioE doctoral students Jasmine Zhou (left) and Karam Khateeb (right). Zhou was lead author of the research team’s paper in Nature Communications. Photos provided by Jasmine Zhou and Karam Khateeb.
This research took place in Yazdan’s Neural Engineering and Rehabilitation Design Lab at the UW and in the Washington National Primate Research Center on the UW campus. The study was led by Yazdan and Jasmine Zhou, a UW doctoral student in bioengineering, with assistance from Karam Khateeb, another UW doctoral student in bioengineering.
“Currently, there are two main treatments for acute ischemic stroke: dissolving the clot with medication or removing it mechanically to restore blood flow. While both methods can be highly effective, many patients cannot receive these treatments because they arrive too late, do not meet eligibility criteria, or lack access to specialized care,” Zhou said. “Our research points to a potential new option that could be delivered in the critical early hours after stroke, when brain injury is still reversible, to help prevent further damage. By preserving vulnerable tissue early on, patients may have a greater chance of recovery, improved independence, and a better quality of life.”
Yazdan and her research team received guidance and support from a number of experts in medicine and engineering, including UW ECE Professor Chet Moritz, who holds joint appointments in rehabilitation medicine, physiology, and biophysics. Moritz is also the co-director of the Center for Neurotechnology, of which Yazdan is a faculty member. UW Professor Emeritus Eberhard Fetz, who is from neurobiology and biophysics and is a member of the Center for Neurotechnology, also contributed his expertise. Another UW contributor to this work was Professor Greg Horwitz, also from neurobiology and biophysics. Horwitz offered guidance and expertise on immunohistochemistry analysis for the research team. Further assistance was provided by the surgeons and veterinarians at the Washington National Primate Research Center.
An unexpected finding with great potential
The red area in the graphic above shows irreversible brain damage after ischemic stroke and, from left to right, how that damage increases significantly within a 24 to 48-hour period without effective treatment. Yazdan and her research team believe that their approach could slow this progression at the earliest stage, shown in the far-left image, and dramatically improve the patient’s chances for recovery. This illustration is from The New England Journal of Medicine, van der Worp HB and van Gijn J, “Acute Ischemic Stroke,” N Engl J Med. 357.6 (2007): 572-579. Copyright © 2007 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
A research breakthrough can sometimes happen unexpectedly, and that was the case with this finding. In 2020, Yazdan was designing experiments at the start of the COVID-19 pandemic that would be safe to conduct in-person while still contributing toward the larger vision for her work. Most of Yazdan’s research focuses on neuroplasticity, the ability of the brain to form and reorganize synaptic connections, especially in response to trauma or injury. With this focus in mind, she and Zhou put together an experiment that would use targeted electrical brain stimulation following stroke to study neuroplasticity.
In the experiment, the research team applied a form of electrical brain stimulation called “theta burst,” which is a rapid, rhythmic pattern designed to influence neural activity directly adjacent to a damaged area in the brain. The team expected to observe the brain’s neuroplasticity in response to the stimulation. But instead, what they discovered was that the electrical stimulation they applied to the brain was reducing neural activity in tissue surrounding the damaged area. This quieting of neurons had an unexpected, neuroprotective effect — significantly reducing lesion volume, inflammation, and cellular stress markers. Remarkably, in some cases, the damaged area of the brain was reduced by almost half.
“This was a notable and unexpected finding, but it was enabled by a series of technologies that were developed in my lab,” Yazdan said. “We had developed technologies that allowed us to monitor the changes in neural activity and blood flow across brain networks with high spatial and temporal resolution.”
Initially surprised by the results of their experiment, Yazdan, Zhou, and their research team followed up with additional experiments and almost three years of data collection and analysis to confirm the findings prior to publishing the results of their study.
Opportunities to impact people’s lives for the better
Yazdan emphasized that although this is a notable advance, the research is still in its early stages, and there is much that warrants further investigation. She has filed for a patent, and she said her next steps will include a longer-term study that could look at changes in function, behavior, and recovery. She would also like to explore the possibilities for this type of electrical stimulation to reduce cortical damage resulting from other kinds of strokes in different areas of the brain. Combining electrical stimulation protocols in various ways for both neuroprotection and neuroplasticity in acute and chronic (long-term) stroke management is something she intends to explore as well in the coming years.
Even with many studies still ahead of her, Yazdan remains focused on evolving this treatment for stroke to the point where it could be used in clinics. She also noted that this stimulation protocol could help to pave a road to new treatments for other types of damage to the nervous system, such as spinal cord injury and traumatic brain injury.
“The number of people that this treatment could impact is really high, and I think that out of all the research I’ve done so far, this work is the closest to translation,” Yazdan said. “That is really exciting to me, the possibility that it could move forward to a point that we see it used in clinical applications. I think it goes back to patient care and the ways we can minimize damage after these types of injuries. This treatment holds great potential to not only improve the quality of life for stroke survivors, but also for their families and caregivers.”
Learn more about this research by reading “Early intervention with electrical stimulation reduces neural damage after stroke in non-human primates” in the journal Nature Communications. More information about professor Yazdan is available on her UW ECE bio page. Funding for this study was provided by many sources acknowledged in the Nature Communications paper, including the Weill Neurohub, which brings together researchers and clinicians at the UW, UC Berkeley, UC San Francisco, and the Allen Institute to speed the development of new treatments for neurological and psychiatric diseases.