Treatment of Traumatic Brain Injury (TBI) with customized polymer-based low volume resuscitation (LVR).
Abstract
Traumatic brain injury (TBI) is a serious condition caused by severe brain concussion and represents a big problem for injured Soldiers. In fact, TBI has recently been called the disease of the Iraq war because of so many injuries from brain trauma. Injured Soldiers have additional problems besides their underlying traumatic injuries from battle. Specifically, they must often spend prolonged times on the battlefield in austere environments after they are injured because of safety concerns during evacuation. Therefore, stabilizing injured Soldiers on the field to greatly expand the safe evacuation time is needed to ensure good outcomes after they reach a forward hospital. Our recent work in blood loss shock resulted in the development of a low volume intravenous (IV) solution that is stable and can be administered in small volumes to dramatically improve the safe time spent waiting for evacuation. The active agent in this solution is polyethylene glycol (PEG), which stops injured tissues from gaining water weight and swelling. This dramatically improves outcomes. Since brain tissue also swells when it is injured, it seems possible that a similar approach can also work for TBI, which often co-occurs with shock on the battlefield. Therefore, it was our goal to make a similar protective solution customized for the brain so that this custom PEG molecule can be added to the existing formulation. This will make an IV solution that does double duty because it can be useful for both shock and TBI. To meet that goal, we have set forth two major aims that we will address by conducting lab studies. Specific Aims: (1) To discover what smaller size of PEG molecule will work best for brain swelling since the brain has a unique and specific circulation that keeps the current PEG agents from working well. (2) To determine the effects of optimized PEG drugs in rat models of TBI and blood loss shock. This mimics what Soldiers experience, so if the new IV formulation works in them, then it should work in Soldiers too. For the first aim, we will do studies in lab rats that are anesthetized where we give different sizes of PEG so we can find a size where about one-third of the drug shows up in the cerebral spinal fluid around the brain and the remaining two-thirds of the drug stays in the blood supplying the brain. This is the size that will optimally prevent the brain from swelling after it is injured and thereby make recovery more successful. After we identify this correct size of PEG molecule, then we will add it to our current solution and try it in rats that have undergone brain injury by a concussion. We will measure brain injury by microscopic pictures of the brain and by how well the rats can recover and perform tests to check motor skills like walking on a balance beam. Then we will compare the results to other rats that get the usual treatment to see if this new solution works. If it does, then we will move on to test it in patients and Soldiers with brain injury due to trauma. Impact: This new approach should improves tolerance to traumatic injury caused by blood loss and head concussion (TBI) and lengthen the time that severely injured Soldiers can safely remain on the battlefield until they need more definitive care at a hospital. This added field time helps medics get them to definitive medical care so that their outcomes will improve and so lives can be saved.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810597
Entities
People
- Martin J Mangino
Organizations
- United States Army
- Virginia Commonwealth University