Claudia Sue Robertson, M.D.; Baylor College of Medicine, Traumatic Brain Injury Multidisciplinary Research Consortium Award

We're trying to work on improving the neurological recovery after traumatic brain injury, particularly people that have suffered a mild traumatic brain injury. We have a lot of treatments now for severe traumatic brain injury but folks with the-that have suffered a mild traumatic brain injury also have problems with memory, with problems keeping attention, problems with headaches and really long-term problems that are debilitating even though the head injury was relatively mild. And that's what we're really trying to come up with some drugs or treatments that can improve the outcome.

Well, TBI is very common, like 4,000,000 people a year that have a mild traumatic brain injury. The military is seeing many, many head injuries, soldiers that are even close to an explosion can suffer a mild traumatic brain injury that can leave them with really debilitating complications.

In our laboratory, the CDMRP funding is looking at a hormone called erythropoietin; this is a protein that is normally produced in the body. It is a hormone that increases red cell production by the kidneys and is also produced in the brain after injury, and it's thought to be one of the endogenous nerve protective responses that the brain has to injury. And when we give this in the laboratory in an experiment of traumatic brain injury, it actually improves the outcome. And so we think that it-we're sort of enhancing what the brain normally-the normal-the brain normally responds to injury by giving this drug. So we're looking at a model of mild traumatic brain injury where the brain injury is complicated by hypotension, a low blood pressure, and this way we're mimicking to let's say a soldier that has mild head injury but also systemic injuries like a broken leg or an abdominal injury where they may become hypotensive along you know as a part of their injury. And the hypotension markedly worsens the brain injury so we're trying to see if this drug, erythropoietin, will protect the brain during the period of hypotension and then that way have a better outcome.

The first year of the grant we spent developing this and characterizing this model of mild TBI followed by hemorrhagic shock, and we fully characterized that and what we found is that a mild head injury that really doesn't cause any consequences for the animal, the recovery is normally-it looks normal; the brain looks normal after the injury, if you follow that by a period of hypotension it makes a very, very severe brain injury. So it's like the brain is just not able to manage the hypotension in the way-the same way that a normal brain is able to. And we're now using this model to look at the effects of erythropoietin. And we're about part way through with these studies and the very early studies look very promising, and then we're also looking at another drug that mimics part of the-it's a peptide that mimics part of the erythropoietin molecule that has the same activities as erythropoietin. Both of these drugs look like they have very protective effects in this model.

In addition to looking at this model, we're going to look at just mild traumatic brain injury alone and see if it's protective after that kind injury. It's a little bit more difficult to model in an animal because a lot of the symptoms that you have in a mild traumatic brain injury are very subjective like headache, dizziness, and things like this that are a little bit harder to test in an animal model. So we've been working on trying to develop some sensitive tests for a model and we'll be looking in the-at the drug in this-in this model.

The TBI multidisciplinary consortium allows us to work together on this problem, and there's several investigators using different models of traumatic brain injury but each with their own special characteristics. And we're each developing sort of a mild version of our head injury model. And it allows us to work together to develop outcome measures that would be useful for these models and we're able to share data and to come up with what we hope will be sort of the best model for mild traumatic brain injury and the best outcome measures for mild traumatic brain injury.