Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sugar entering the brain during septic shock causes memory loss

23.04.2019

Research gives clear target for drug development and further study into memory loss

The loss of memory and cognitive function known to afflict survivors of septic shock is the result of a sugar that is released into the blood stream and enters the brain during the life-threatening condition.


Memory loss and cognitive dysfunction associated with septic shock is the result of the sugar heparan sulfate, which is released into the bloodstream and enters the brain during the life-threatening condition.

Credit: Rensselaer Polytechnic Institute

This finding, published today in the Proceedings of the National Academy of Sciences, explains the premature mental aging that follows septic shock and may shed light on memory loss in other diseases.

"This sugar is getting into the hippocampus, and it shouldn't be in there," said Robert Linhardt, professor of biocatalysis and metabolic engineering at Rensselaer Polytechnic Institute, and lead author of the study. "We actually think this is rewiring memory in the hippocampus, and it's causing memory loss. Neural circuits are being disrupted or broken or connected in the wrong way."

The study is the latest outcome of a six-year partnership between Linhardt and Dr. Eric Schmidt, an expert on sepsis and assistant professor in the Department of Medicine at University of Colorado Denver.

Sepsis is a systemic infection of the body. One-third of patients admitted to hospitals with sepsis go into septic shock. Of those, half will die. In a 2016 study published in the American Journal of Respiratory and Critical Care Medicine, a team that included Schmidt and Linhardt developed a simple but accurate test for determining whether patients in septic shock would recover or die.

The test uses a urine sample to check concentrations of a type of sugar - glycosaminoglycans - that ordinarily coat cells lining blood vessels and other surfaces inside the body. In septic shock, the body sheds fragments of these sugars, and the team found that higher concentrations portend death. The test is used in clinical settings, and the insight has helped doctors search for more effective therapies.

Their next step tested whether a link exists between the sugars and mental aging associated with septic shock. Research published in the February edition of the Journal of Clinical Investigations showed that, during septic shock, fragments of the sugar heparan sulfate crossed the blood-brain barrier and entered the hippocampus, a region of the brain critical to memory and cognitive function.

Evidence indicated that the heparan sulfate might be binding with brain-derived neurotrophic factor (BDNF), which is critical to hippocampal long-term potentiation, a process responsible for spatial memory formation. The researchers also found that presence of an enriched heparan sulfate in the blood plasma of septic patients upon admission to an intensive care unit predicted cognitive impairment detected 14 days after discharge.

To be sure, the researchers wanted to see the heparan sulfate enter the hippocampus and bind with BDNF. The new study in PNAS shows exactly that. To follow heparan sulfate into the brain in a sea of other sugars moving through the bloodstream Linhardt's team had to synthesize heparan sulfate tagged with a stable carbon isotope, which unlike many other labeling methods, is completely safe and was identical to the natural sugar. It took them two years to figure out how to do it.

Then they put their hypothesis to the test. In healthy mice, 100 percent of the tagged heparan sulfated was excreted through the urine within 20 minutes, and none ever entered the brain. But in septic mice, researchers found a small amount of tagged heparan sulfate in the hippocampus region of the brain.

"Now that we know the cause of cognitive damage in septic shock, it gives us a clear target for a drug therapy: something that binds to the sugar and clears it, or an enzyme that converts it to something that won't impair cognitive function," Linhardt said. "This is an important advance, and we're excited about the story that's unfolding."

###

At Rensselaer, Linhardt is joined in the research by Xing Zhang and Xiaorui Han. At University of Colorado, Schmidt is joined by Yimu Yang, Kaori Oshima, Sarah Haeger, Mario Perez, Sarah McMurtry, Joseph Hippensteel, Joshay Ford, and Paco Herson. The current research also includes Linhardt's former student, Jian Lu, now on the faculty at the University of North Carolina at Chapel Hill, and his colleague, Yongmei Xu, who led in the synthesis of the tagged sugar.

About Rensselaer Polytechnic Institute

Founded in 1824, Rensselaer Polytechnic Institute is America's first technological research university. Rensselaer encompasses five schools, 32 research centers, more than 145 academic programs, and a dynamic community made up of more than 7,900 students and over 100,000 living alumni. Rensselaer faculty and alumni include more than 145 National Academy members, six members of the National Inventors Hall of Fame, six National Medal of Technology winners, five National Medal of Science winners, and a Nobel Prize winner in Physics. With nearly 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on addressing global challenges with a spirit of ingenuity and collaboration. To learn more, please visit http://www.rpi.edu.

Media Contact

Reeve Hamilton
hamilr5@rpi.edu

 @rpinews

http://news.rpi.edu/ 

Reeve Hamilton | EurekAlert!

More articles from Health and Medicine:

nachricht Mutations in donors' stem cells may cause problems for cancer patients
17.01.2020 | Washington University School of Medicine

nachricht Overactive brain waves trigger essential tremor
17.01.2020 | Columbia University Irving Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Miniature double glazing: Material developed which is heat-insulating and heat-conducting at the same time

Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.

Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...

Im Focus: Fraunhofer IAF establishes an application laboratory for quantum sensors

In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.

The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...

Im Focus: How Cells Assemble Their Skeleton

Researchers study the formation of microtubules

Microtubules, filamentous structures within the cell, are required for many important processes, including cell division and intracellular transport. A...

Im Focus: World Premiere in Zurich: Machine keeps human livers alive for one week outside of the body

Researchers from the University Hospital Zurich, ETH Zurich, Wyss Zurich and the University of Zurich have developed a machine that repairs injured human livers and keep them alive outside the body for one week. This breakthrough may increase the number of available organs for transplantation saving many lives of patients with severe liver diseases or cancer.

Until now, livers could be stored safely outside the body for only a few hours. With the novel perfusion technology, livers - and even injured livers - can now...

Im Focus: SuperTIGER on its second prowl -- 130,000 feet above Antarctica

A balloon-borne scientific instrument designed to study the origin of cosmic rays is taking its second turn high above the continent of Antarctica three and a half weeks after its launch.

SuperTIGER (Super Trans-Iron Galactic Element Recorder) is designed to measure the rare, heavy elements in cosmic rays that hold clues about their origins...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

„Advanced Battery Power“- Conference, Contributions are welcome!

07.01.2020 | Event News

 
Latest News

A new 'cool' blue

17.01.2020 | Life Sciences

EU-project SONAR: Better batteries for electricity from renewable energy sources

17.01.2020 | Power and Electrical Engineering

Neuromuscular organoid: It’s contracting!

17.01.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>