Spring 2021

THRIVING

For Dr. Ukpong Eyo, Neurological Research isn’t just Professional, it's Personal
by Keith Jones, iTHRIV Communications Coordinator

“These cells aren’t in the brain at the first stages of development, they move up and migrate to the brain…they’re like me, an immigrant” muses Dr. Ukpong Eyo, PhD. Speaking about microglia, immune cells that reside in the brain, he states “I feel a connection to this research, I want to find out what role microglia play in brain function”. Dr. Eyo is seeking to understand how the microglia help manage brain function through vascular regulation as well as in seizure disorders.

Based on the strength of his initial findings Dr. Eyo has received qualifying scores on two new NIH R01 grant applications to study microglia in depth. The combined grants will total $5M over five years.

The brain accounts for only about 2% of our body’s weight, however it utilizes up to 20% of the body’s energy which is mostly delivered through the blood circulation of oxygen and nutrients. The brain, therefore needs a constant and consistent supply of blood and well-functioning blood vessels. Neurological pathologies, such as Alzheimer’s disease have a connection with impaired blood vessel function. Dr. Eyo’s research seeks to determine what, if any, effect microglia have on blood flow in the brain. “If you’re looking for microglia in the brain, there is a good chance you will find them on a blood vessel”, says Dr. Eyo.  His previous research indicates that about a third of the brain’s microglia are concentrated around blood vessels, and Dr. Eyo intuits that “they most likely play an important role in neurovascular function”. 

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Dr. Eyo at a microscope in the lab

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Microglia in the brain (green) as well as the vasculature (magenta). Some microglia are associated with the vasculature (arrows). 

To test his hypothesis, Dr. Eyo used pharmaceuticals to eliminate microglia in the brain. This approach targeted both vessel-associated and non-vessel-associated microglia. The study yielded remarkable results; the size of the blood vessel changed and this corresponded to a change in the amount of blood flowing into the brain. Dr. Eyo’s study seems to suggest that microglia can be manipulated to regulate blood flow. The findings are important, as this is indicates the possibility for a new approach to resolve impaired blood flow function in diseases such as Alzheimer’s disease.

Dr. Eyo has designed a three step study for the first project. He and his investigative team will seek to determine whether all the microglia mediate the blood vessel/blood flow changes, or if it is specifically the vessel-associated microglia that control this function. In the second stage, the researchers will determine whether microglia perform this function directly or indirectly by instructing an intermediate cell type, the astrocyte. Finally the team will determine whether these findings are relevant for blood vessel flow regulation in a mouse model of Alzheimer’s disease.

His second project has a deeply personal connection. Dr. Eyo relates that his son endured several febrile seizure events before he reached three years of age. Febrile seizures are the most common form of childhood seizures. They affect 2-5% of children from age six months up to five years. The underlying mechanisms are not fully understood, but febrile seizures occur with a rise in body temperature that is often associated with a fever. Though the seizures are benign, physical effects of the seizure can lead to ancillary injury. In preliminary studies, the team developed a mouse model of febrile seizures. The researchers noted that with increased temperatures, the test mice showed seizures. Mice whose microglia were eliminated experienced more severe seizures, suggesting that microglia may play a mitigating protective role against seizures.

Like his other project, this study will include a three step process. Dr. Eyo explains, for “the first part we will use more specific approaches to eliminate microglia and determine whether this would actually worsen the seizures.” Dr. Eyo clarifies that “previously, we could only remove cells that look like microglia without sufficient specificity”. The second part of the study is designed to identify whether or not there is a specific microglial protein that regulates the beneficial role of microglia in seizures. If this protein is identified, it could lay the groundwork for future studies to target this protein to modulate seizures in patients. The final part will be to determine whether targeting microglia and this protein receptor could prevent the incidence epilepsy in adulthood following temperature-induced seizures.

 

When not in the lab, Dr. Eyo serves as one of a select group of Scholar mentors leading the mentor training program with the integrated Translational Health Institute of Virginia (iTHRIV). The iTHRIV Scholars Program combines structured mentoring sessions, career development, and a core curriculum. Additionally, Scholars and mentors are connected to researchers and resources from across the iTHRIV partner sites. “It is truly amazing to have a program dedicated to fostering career development for early career researchers. This program seeks out talented researchers and connects them to the resources they need to succeed”. Dr. Eyo is paired with current iTHRIV Scholar Dr. Kaitlin Love and is looking forward to lending his perspective as an accomplished basic scientist. “Far too often in research we are silo-ed. We should break those barriers, when the clinical side communicates with the basic science side everyone benefits”.

 

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Dr. Eyo with is (now 8 year old) son who had febrile seizures earlier in life

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