Activating T Cells Could Improve Neurological Outcomes After Cardiac Arrest

Despite advancements in cardiopulmonary resuscitation (CPR) and improved hospital access, survival rates after out-of-hospital cardiac arrest (OHCA) remain low, with only about 10% of patients surviving. After reaching the hospital, most individuals who survive the initial cardiac arrest succumb to brain injury, and there are currently no medications available to prevent this outcome. Researchers have now identified a specific group of cells that could potentially offer protection against brain damage following cardiac arrest, prompting them to explore a drug that activates these cells to improve neurological recovery.

A team of researchers from Mass General Brigham (Somerville, MA, USA) studied samples from OHCA patients and discovered changes in immune cells just six hours after cardiac arrest that could predict brain recovery 30 days later. They identified a particular population of cells that might offer protection from brain injury and a drug that can activate these cells, which they tested in preclinical models. The research followed their observation that while some cardiac arrest patients showed elevated inflammation during their first night in the hospital, they showed rapid improvement thereafter. In contrast, other patients continued to deteriorate and eventually died. To understand why some patients survived while others did not, the team began collecting a biobank of cryopreserved cells, donated by patients with consent from their families, just hours after their cardiac arrest. Using single-cell transcriptomics, they examined gene activity in the cells.

The findings, published in Science Translational Medicine, revealed that one group of cells, called diverse natural killer T (dNKT) cells, was elevated in patients who showed favorable neurological recovery. These cells seemed to play a protective role in preventing brain injury. To further explore this, the team treated mice with sulfatide lipid antigen, a drug that activates these protective NKT cells, following cardiac arrest. The mice demonstrated improved neurological outcomes. While the researchers acknowledge the limitations of mouse models, they believe that insights from human samples first could enhance the likelihood of successfully translating their findings into effective treatments for patients. Additional preclinical studies are necessary, but their ultimate goal is to move toward clinical trials to determine if the drug can protect against brain injury when administered soon after cardiac arrest.

“Cardiac arrest outcomes are grim, but I am optimistic about jumping into this field of study because, theoretically, we can treat a patient at the moment injury happens,” said co-senior and corresponding author Edy Kim, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital. “This represents a completely new approach, activating T cells to improve neurological outcomes after cardiac arrest. And a fresh approach could lead to life-changing outcomes for patients.”