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New knowledge on preventing brain damage after cardiac arrest
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New knowledge on preventing brain damage after cardiac arrest

Despite improvements in CPR and patient hospitalization rates, only about 10% of people survive after out-of-hospital cardiac arrest (OHCA), resulting in approximately 300,000 deaths per year in the United States. . Once in hospital, most cardiac arrest patients die from brain injury, and no medications are currently available to prevent this outcome. A team led by researchers at Mass General Brigham is seeking to solve this problem. Using samples from patients who had undergone OHCA, the team discovered changes in immune cells just six hours after cardiac arrest that may predict brain recovery 30 days later. They identified a particular population of cells that could provide protection against brain injury and a drug capable of activating these cells, which they tested in preclinical models. Their results are published in Scientific translational medicine.

“The outcomes of cardiac arrest are grim, but I am optimistic about getting into this area of ​​study because, in theory, we can treat a patient at the time the injury occurs,” said Edy Kim, MD, PhD, co-author and corresponding author of the study. Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham Health System. “Immunology is an extremely powerful way to deliver treatment. Our understanding of immunology has revolutionized cancer treatment, and we now have the opportunity to apply the power of immunology to cardiac arrest.”

As a resident physician at Brigham’s cardiac intensive care unit, Kim noticed that some cardiac arrest patients had high levels of inflammation their first night in the hospital and then improved quickly. Other patients would continue to decline and eventually die. To understand why some patients survive and others don’t, Kim and his colleagues began creating a biobank, a repository of cryopreserved cells donated by patients with their families’ consent just hours after their cardiac arrest.

The researchers used a technique known as single-cell transcriptomics to examine gene activity in each cell in these samples. They found that a population of cells – known as diverse natural killer T (dNKT) cells – increased in patients who would have a favorable outcome and neurological recovery. The cells appeared to play a protective role in preventing brain damage.

To test this further, Kim and colleagues used a mouse model, treating mice after cardiac arrest with lipid antigen sulfatide, a drug that activates protective NKT cells. They observed that the mice had improved neurological outcomes.

The researchers note that there are many limitations to mouse models, but making observations from human samples first could increase the likelihood of successfully translating their findings into an intervention that can help patients. More studies in preclinical models are needed, but their long-term goal is to continue clinical trials in humans to see if the same drug can provide protection against brain damage if administered soon after cardiac arrest.

“This represents a completely new approach, activating T cells to improve neurological outcomes after cardiac arrest,” Kim said. “And a new approach could lead to life-changing results for patients.”