Ev McClendon, Ph.D., neuroscientist (and sheep OBGYN), featured in OHSU In the Lab

Stephen Back and Ev McClendon,

Premature babies are at risk for disabilities that can last a lifetime. With sheep from a local farmer, Ev McClendon, Ph.D., has made some groundbreaking discoveries about what causes these cognitive and learning problems — and what might be done to prevent them. A neuroanatomist working in the lab of Stephen Back, M.D., Ph.D., McClendon was the lead author on a recent paper that demonstrated low oxygen, more than low blood flow, causes major disturbances in brain development.

What are you studying and why is it important?

If we can understand what causes brain damage in premature infants, we can do something to prevent it. I look at the development of brains in newborns. In just the last decade, our understanding of early birth and brain development has come a long way. We knew that premature infants have smaller brains than full-term babies and we thought that this was because they were missing neurons. Indeed, with severe brain injury, it was easy to see that portions of the brain were missing. Consequently, it was logical to assume that in brains with milder, less obviously injuries, smaller brain volumes equated with fewer neurons. The previous dogma was that the neurons had died because there wasn’t enough blood flowing to the brain. Although limited blood flow can certainly contribute to maturational changes in the developing brain, it isn’t the only factor. One of the important discoveries in Dr. Back’s lab a few years ago was that the neurons in these small brains weren’t missing, they were underdeveloped. When I learned that all the players — the neurons you expect to find — were there, the next step was to find out why the brain was so small.

What’s been your most exciting moment of discovery?

When I started looking at the anatomy of the neurons in those small brains, I found that the dendritic arbors — the branches on the tree of the brain — weren’t as complex as the branches in normal brains. That was a pretty exciting outcome because it opened the door to possible therapies. All of our discoveries are exciting, since each have clinical implications. Our most recent finding, that low oxygen states alone are sufficient to cause maturational changes, can help provide clinical strategies for treating newborns. Our next step is to find out when and how much oxygen infants need so that we can provide the proper amounts. Too much oxygen can cause other kinds of damage to the infant’s body.

What’s your day-to-day life as a researcher like?

I like to joke that, in addition to being a neuroscientist, I’m a sheep OBGYN. We use a fetal sheep model in our research. The cool thing is that a lot of the sheep breeds have a high incidence of twin pregnancies. That allows us to take advantage of an internal control as far as the mom is concerned. One fetus can act as a control and the other can be the experimental animal. We don’t have just an animal to animal comparison, but an in utero comparison. We have a local farmer who time breeds her sheep on a particular schedule for us. When the ewes are two thirds of the way through their gestational period, I bring the ewes into surgery and place instruments on the fetuses so that I can take measurements later in the gestation period, and manipulate fetal blood flow and oxygenation. After recovery from the surgery, I connect the fetal lines to equipment that lets me monitor blood pressure, heart rate, and changes in arterial blood gases and electrolytes in response to the experimental manipulations. Eventually the brains are harvested to examine the impact of the experiment on neuroanatomy and physiology. Then? I crunch a lot of data.

About In the Lab

OHSU In the Lab publishes every third Thursday on O2 (login required). The series looks at the people in the laboratories who help make OHSU such a vibrant research institution. In each post, researchers describe their current work and answer the same three questions.