Treatment of Spinal Cord Ischemia with Cell Impermeant-Based Resuscitation
Abstract
Spinal cord injury (SCI) is a serious condition caused by severe spinal trauma and represents a big problem for injured Soldiers. In fact, SCI can often result in total or partial paralysis or even loss of life. 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 spinal cord tissue also swells when it is injured, it is reasonable to assume that a similar approach can also work for SCI, which often co-occurs with shock on the battlefield. Therefore, it was our goal to make a similar protective solution customized for the spinal cord so that this custom PEG molecule can be added to the existing formulation. Customization is necessary because the neural tissues in the brain and spinal cord act differently to PEG polymers, so a smaller molecule is needed for the spinal cord to achieve the same benefits that the larger PEG polymers provide elsewhere in the body. This will make an IV solution that does double duty because it can be useful for both shock and SCI. 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 spinal cord swelling since this tissue 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 traumatic SCI 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. Measured outcomes will include paralysis and recovery times. For the first aim, we will do studies in lab rats that are anesthetized and given 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 spinal cord and the remaining two-thirds of the drug stays in the blood supplying the cord. This is the size that will optimally prevent the spinal cord 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 containing the much larger PEG drugs and try it in rats that have undergone traumatic SCI. We will measure SCI by microscopic pictures of the spinal cord and by how well the rats can recover and perform movement tests to check motor function of their hind legs. 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 SCI due to trauma. This whole process from rats to patients may take 5 years of development time. Impact: This research proposal addresses the Fiscal Year 2016 Spinal Cord Injury Research Program Area of Encouragement titled “Pre-hospital, en route care, and early hospital management of SCI.” This new approach should improves tolerance to traumatic injury caused by blood loss and spinal cord trauma and significantly lengthen the time that severely injured Soldiers can safely remain on the battlefield until they need more definitive care at a forward hospital. This added field time helps medics get them to definitive medic
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710602
Entities
People
- Martin J Mangino
Organizations
- United States Army
- Virginia Commonwealth University