Exploring how brain inflammation after stroke can be shaped to support recovery

University of Kentucky College of Medicine researcher Ann Stowe describes her career path as nontraditional. After earning a bachelor's degree in fine arts, Stowe decided to pursue graduate study in biomedical research instead of art history.

Today, the associate professor in UK's Department of Neurology studies how the brain recovers from stroke. The same passion for creativity that attracted Stowe to studying the arts is what drives her in the laboratory.

I believe biomedical research was even more creative from a 'designing my own experiments' point of view. It's a creative output that I knew would hold my attention for a full career."

Ann Stowe, researcher, University of Kentucky College of Medicine

Stowe has made many contributions to stroke research, with her experiment design playing a big role. She came to UK from University of Texas Southwestern Medical Center in 2018 and is now a faculty member in UK's Kentucky Neuroscience Institute and Center for Advanced Translational Stroke Science.

Stowe's research focuses on the inflammation that happens in the brain after a stroke. This interest was piqued during her first journal club meeting in graduate school at the University of Kansas.

"We reviewed a clinical trial that focused on blocking inflammation after a stroke in stroke patients, and it was a profound failure," Stowe said. "From that point on, I've had the theory that brain inflammation is actually required for stroke recovery. It's not all detrimental."

Stroke occurs in the brain when blood flow to an area stops either through a blockage of the blood vessel or the blood vessel rupturing and blood leaking out. Depending on where it happens in the brain, the stroke patient can develop a disability.

Stowe's research goal is to understand how inflammation after stroke can be shaped to support rewiring in the brain and recovery of function that might be lost with injury.

"When you think about the brain and how it reorganizes after stroke, there are many areas that are involved," Stowe said. "It's the other areas of the brain that survived the stroke that actually rewire and reorganize to support recovery. Inflammation can actually affect these other areas, too."

Because they can be critical for functional recovery, focusing on the areas of the brain affected by inflammation after a stroke could lead to possible therapeutic avenues for stroke patients. Currently, there are only two FDA-approved treatments for acute stroke and no effective therapeutics to promote long-term repair in the brain after stroke damage.

Stowe's current research focuses on the immune system's response to stroke. One of her recently published studies shows that after stroke, B cells migrated to regions of the brain known to generate new neuronal cells and regulate cognitive and motor functions – another indication that targeting other areas of the brain after stroke could be promising for drug development.

"This study suggests that B cells might have a more healing role," Stowe said. "Hopefully from this, we can better understand the inflammatory processes after stroke – and long term, possibly identify what subsets of immune cells can support stroke recovery."

Stowe is currently working on understanding how different B cell types either inhibit or support recovery, as other labs have shown that antibodies from B cells contribute to post-stroke dementia. Identifying and supporting beneficial B cell types is fundamental to developing new and effective therapies.

She says redesigning experiments is a creative process – the outcome of each study is important to drive research forward, whether or not a hypothesis can be proved.

"I think we tend to love what it is that we're studying, hopefully. And we tend to really love what our hypothesis is and think we should be proving that," she said. "But it's much better to try to be unbiased and objective because however it turns out is important. I'm not always correct, but then we redesign the experiment. Going back to the creativity aspect of science – that is by far the most fun that I have."

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