Sharon Leah Juliano, Ph.D.; Uniformed Services University of the Health Services; Intramural TBI Investigator-Initiated Research Award

We're looking at traumatic brain injury and we're particularly interested in how to potentially heal brain injury by the use of stem cells. And we're hoping to get stems to particularly migrate into the region of the injured brain and re-establish a circuit there so we can get the cells kind of back in the order to the way they were before the injury happened. Most traumatic brain injuries involve the cerebral cortex. The cerebral cortex as you may know is the highest part of the brain so that's where we do most of our thinking and thoughts and so forth. And there are particular populations of cells that migrate into or populate the cerebral cortex so we're interested in those particular populations of cells. We're making stem cells from these populations of cells and we're using what are called organotypic cultures as hosts for the stem cells. And we're trying to see how the stem cells behave and how they migrate into cerebral cortex. This is a picture of one of these organotypic cultures and we found that if we inject them into this culture, or sort of place them, you know normal organotypic cultures the cells move all over the place. They go throughout the extent of the cerebral cortex, which is again this outer most part of the brain. But what we found when we do this same experiment in the wounded cortex or the injured cortex the cells migrate directly into the injured spot. It was quite amazing that they just are specifically attracted to that particular site. As the cerebral cortex develops cells migrate into their proper place. And we can hopefully use these principles of understanding development to further understand how to use these cells to heal the injured brain when we have something like a traumatic brain injury. This is a very young developing cerebral cortex. The cells are generated in this region and then they have to move all the way into the cerebral cortex, so they're moving in what's called the tangential way and they don't have a particular scaffold or something to lean on to get there. But these cells in the matricular zone are migrating in what we call radially. It's much shorter and they also have a scaffold to lean on that you can't really see in this picture. If we use these guys to transplant into our host cultures, the cells that come from here migrate much more extensively and they reach the higher parts of the cerebral cortex more effectively than the cells that come from here. And this is kind of interesting because it just means that they're overall better migraters and that they get to go where we want them to go much more easily. And that kind of information is indicated on these graphs over here. We knew from previous studies some other people have done, these cells that are migrating into the cortex are attracted there. There are factors in the cerebral cortex that are attracting these cells, that are giving them cues to say "OK, go in this direction and go over here to this particular spot." What we have been able to do is sort of extract proteins from the cerebral cortex and divide them up into different fractions and then look at this population of cells from the ganglionic eminence and see which fractions they prefer. So this was one of the main points of working on this project is to identify these attractive proteins and use them in our transplantation studies to help heal traumatic brain injury and to get the cells into where they want go. The other thing that's really important to use is to look at these regions that have attracted these cells and to see what's going on in there. Are they forming functional circuits? Are they connected appropriately to other neurons? Do they project out into the surrounding cortex? So we've got a lot to do that's very exciting, I hope.