Tulane University researcher Olan Jackson-Weaver received a $1.6 million grant from the National Institute of General Medical Sciences in the National Institutes of Health in 2024. With this grant, Weaver and his team continued to study the causes of blood loss in patients who suffered from trauma.
“There’s this really interesting …[but] devastating phenomenon that happens in trauma patients, where … this protein and sugar lining of all the blood vessels in trauma patients and in other critical illness patients, it actually gets shed off … into the bloodstream,” Weaver said. “That ends up causing a lot of problems with coagulation. The blood doesn’t clot as good as it should.”
This lining is called the endothelial glycocalyx, and without it, trauma patients experience excess blood loss and inflammation.
“Once we understand that,” Weaver said, “the hope is we can figure out a way to stop it from happening in these patients.”
Research methods
Weaver and his team used three levels of research throughout the study. First, Weaver and his team culture vasculature cells in the lab. Using basic methods of biochemistry, the lab can study the endothelial glycocalyx in depth.
“That gives us a lot of power to really dissect the mechanism,” Weaver said. “We can see this layer, the glycocalyx, being shed in the cultured cells … so we can mess with the process. [We can try] of different techniques to figure out how it’s working.”
After studying the cultured cells, the next step is using live samples: rat models.
“We anesthetize rats, and we can put vascular lines in their femorals, femoral arteries and jugular vein, and we can do a controlled hemorrhage,” Weaver said.
These rat models, which mimic a typical trauma patient who might arrive at a hospital, can then be resuscitated to watch the endothelial glycocalyces shed. Once the linings are shed, the rats are euthanized, allowing the lab to study their tissu.
Lastly, Weaver and his team use real trauma patient blood samples from the Norman E. McSwain, Jr. MD, Spirit of Charity Trauma Center, the first Level 1 Trauma Center in New Orleans, to confirm the findings from the previous two levels of research.
“We get blood samples from trauma patients when they get to get to the emergency department,” Weaver said, “and we can study … the shedding in that plasma sample.”
Though the official paper is yet to be finished, Weaver suggests that the answer to the six-year-long study might have been sitting in plain sight all along.
The solution is simple: Keep the membrane fluid.
“That compound [for maintaining membrane fluidity] is called DMSO. It’s actually just a common solvent we use in the lab. We don’t consider it a drug in itself,” Weaver said. “But it’s looking promising, if the data keeps going the way we think it’s going.”
Dimethyl sulfoxide is a byproduct of paper-making that is approved by the Food and Drug Administration for one condition: bladder inflammation. When given to animal models, DMSO is shown to resolve coagulopathy as well as better lungs damaged by hemorrhages. Being FDA-approved makes it easier for Weaver and his team to propose its use in another setting.
This breakthrough is just the beginning. Weaver plans to not only figure out how to prevent glycocalyx damage in trauma patients but also find out how to regrow the glycocalyx.
Furthermore, his research also points to a correlation between estrogen and protection from endothelial glycocalyx shedding.
“We’ve been finding a very interesting difference between male and female animals … and it looks like we’re seeing something similar in the trauma patients,” Weaver said. “Women have some amount of protection against this glycocalyx damage, so … [that] effect of estrogen is fascinating, and that’s something we’re going to look into for sure.”
Beyond trauma, glycocalyx damage may also occur during organ transplants.
“If that’s true,” Weaver said, “then maybe we can give some of the same treatments to these transplanted organs to help improve the organ survival during transplantation.”
With the help of the Tulane surgery department and trauma team as well as the Tulane University School of Medicine, Weaver and his team will soon conclude the study.
“Just keep plugging away at it and trust that at some point you’ll break through,” Weaver said. “And we did, finally, after a lot of struggles. We finally got funding for it, and finally got a big publication out of it, and now we’re kind of off and running.”