Too much sugar in the bloodstream can worsen septic shock, lead to memory loss

Survivors of septic shock often experience memory loss and premature cognitive decline. While this is a known and established occurrence, the cause of this cognitive impairment is unknown. But in a new study published in The Proceedings of the National Academy of Sciences, American researchers finally shed light on what causes the loss of cognitive function that follows septic shock. They pinpointed a complex sugar called heparan sulfate as the main culprit and showed that it selectively targets and enters the hippocampus, where it wreaks havoc on neural circuits and causes problems with spatial memory formation.

What is septic shock?

Septic shock is a serious condition that occurs when the blood pressure of a person with sepsis drops too low. During sepsis — the body’s extreme response to an infection —  the immune response goes out of control and causes damage to several organs. This, in turn, disrupts their normal functioning and often renders these organs dysfunctional or even nonfunctional. According to statistics, about one-third of patients with sepsis who are admitted to hospitals go into septic shock, and half of them eventually die.

Patients with sepsis usually experience a drop in blood pressure. However, if a patient’s blood pressure doesn’t normalize in time, his or her body can go into septic shock. Those who go into shock need to be treated immediately. Low blood pressure limits the amount of oxygenated blood that reaches the vital organs. When organs don’t get sufficient oxygen from the blood, they will start to fail. Septic shock has life-altering consequences and is potentially fatal, so knowing how to recognize and prevent it is important. (Related: TCM found to improve blood flow in septic shock patients.)

The role of heparan sulfate in cognitive impairment after septic shock

According to the researchers, sepsis causes the release of heparan sulfate from the glycocalyx of epithelial cells. The glycocalyx is a carbohydrate-rich layer attached to the cell membrane. When heparan sulfate is released into the bloodstream, these sulfur-containing compounds make their way to the brain. What’s surprising is that they don’t invade other parts of the brain except for the hippocampus. The hippocampus is involved in many processes related to cognition, such as memory formation, learning, and emotional processing. The researchers surmised that heparan sulfate molecules somehow impact spatial memory formation.

In a continuation study, which appeared in The Journal of Clinical Investigations, the same researchers conducted another experiment on mice with induced sepsis. They observed that sepsis survivors experienced loss of long-term potentiation (LTP) in the hippocampus. LTP has to do with synaptic activity and signal transmission between neurons. It is also important for spatial memory formation. LTP is mediated by a molecule known as brain-derived neurotrophic factor (BDNF). However, the researchers found that preserving BDNF content doesn’t stop memory impairment in mice. On the other hand, stimulating BDNF signaling could reverse the impairment, suggesting that there is a molecule present in the hippocampus that inhibits BDNF activity.

The researchers soon learned that, during sepsis, heparan sulfate fragments that reach the hippocampus bind to BDNF to prevent LTP. When they looked at the structure of the fragments, they found a pattern of sulfation (sulfur attachment) that’s conducive to BDNF binding. The researchers also found the same sulfation patterns in the plasma of patients with sepsis who were at an intensive care unit (ICU). These patterns helped predict persistent cognitive impairment in the patients 14 days after they were discharged. Based on their findings, the researchers concluded that heparan sulfate — especially with a specific sulfation pattern — in the blood is responsible for the cognitive decline experienced by survivors of septic shock.

Health.news has more info about septic shock and effective ways to prevent it.

Sources include:

Newswise.com

MedicalNewsToday.com

PNAS.org

VeryWellMind.com

JCI.org