How can stroke recovery be improved?

Teena Joy speaking at the 7th Annual JAX Scientific Symposium at The Jackson Laboratory for Genomic Medicine. Photo credit: Cloe Poisson Mary Teena Joy speaking at the 7th Annual JAX Scientific Symposium at The Jackson Laboratory for Genomic Medicine. Photo credit: Cloe Poisson

Neuroscientist and JAX Assistant Professor Mary Teena Joy investigates what happens to the brain after a stroke and how to enhance brain neural rewiring to improve recovery.

Coming full circle

Teacher, astronaut, doctor. If you asked a group of elementary school students, ‘What do you want to be when you grow up?’, these are some of the responses you might expect to hear. In second grade, Mary Teena Joy, Ph.D., was certain she wanted to be surgeon. More specifically, Joy envisioned herself as a heart surgeon who also would go on to cure those affected by human immunodeficiency virus (HIV).

“I think I have always wanted to help people, especially during recovery from an illness, infection or event,” says Joy.

Joy’s compassion eventually led to her current research focus, stroke and neurological disease. But don’t worry, her childhood dreams haven’t gone unfulfilled. After graduating with a Ph.D. in neuroscience, Joy’s postdoctoral work played a key role in the identification of a key target for stroke recovery, which is also used to treat HIV by lowering the amount of virus found in the blood.

“I didn’t foresee myself repurposing a HIV drug for stroke with the research I was doing at the time,” says Joy. “I’m glad I was able to experience how impactful research can be in the clinic, and I plan to implement similar framework in my lab as we investigate how we can get brain circuits to remodel after a stroke.”

Stroke: the known and the unknown

What happens when you have a stroke? A stroke event is caused by bleeding (hemorrhagic) or blockage (ischemic) disruptions to the brain’s blood supply. These can take place as one big event or a series of smaller attacks causing temporary disruptions to blood flow, also known as mini strokes. A leading cause of death and disability globally, Joy took interest in this topic when studying axon regeneration in models of spinal cord injury.

“Think of axons as cables of transmitting information between different regions in the brain and the spinal cord and this information is what generates actions and how we interact with the world,” says Joy. “What I learned was that we can get axons to regrow, but they do not necessarily make functional connections that are important for recovery. This caused me to consider the plastic environment in the brain after a stroke and treatments that harness this existing plasticity for functional rewiring to restore function.”

Molding minds

Brain plasticity gives rise to structural and functional changes in the brain. Humans experience the most brain plasticity from childhood to young adulthood. While the extent of plasticity reduces with age, it remains active into adulthood as we learn new things or have novel experiences.

“During the first three months after a stroke, patients experience what is called a ‘window of plasticity,’ a critical time of heightened restructuring for the surviving parts of the brain,” says Joy. “If therapies are implemented during this stretch of time, patients have been shown to improve with greater success than those treated later.”

The brain possesses the ability to rewire itself to adapt to the recent cellular damage caused by the lack of blood flow. It’s far from perfect, however. Researchers like Joy are working to identify both the beneficial and non-beneficial healing pathways the brain incorporates following a stroke event.

“By identifying the adaptive and maladaptive mechanisms the brain uses to rewire following a stroke, we may be able to intervene and correct the poor circuitry from being implemented,” says Joy.

Firing on all cylinders

Despite better medical interventions such as clot removal devices and neurorehabilitative training, patients are left with long-lasting impairments that affect their daily living.  A key reason for lack of effective therapies for stokes is because we need more studies that integrate circuit, molecular and behavioral output.

“By understanding circuit rewiring, the genes that drive rewiring and the consequence of these computations in the brain on motor actions, we can then device therapeutics that target these systems,” says Joy.

Using cutting-edge technology, Joy and her team can visualize in real-time neurons firing in large swaths of the brain in animal models performing different motor behaviors. Her lab uses that data to better understand brain circuit function or dysfunction as well as molecular pathways playing a role in these processes.

Joy’s work relies on using machine learning to not only predict recovery responses from gene expression profiles, but also to use it to quantify behavioral changes as a result. Joy believes this will lead to identification of novel drugs and neurostimulation therapies for stroke recovery.

“We work closely with both the computational and fabrication teams to build custom automated systems to capture the most accurate and applicable data,” says Joy. “This was something I never thought possible prior to coming to JAX.”

Collaboration, innovation and fun are what Joy intends to ingrain into her lab as she moves forward in her new role. She credits much of her success to the great mentors she’s had along the way and hopes to fill that role for other up-and-coming scientists.

“In this career path, people get to know your success, but there is a lot of rejection along the way. You cannot dwell on the failures. Find what keeps you excited and pursue it.”