Grant: Project Grant

We have all heard someone say, "Grandma (or Grandpa) was never quite the same after surgery." Among older adults, one of the most common and debilitating complications after surgery is a decline in brain function. Healthcare providers refer to such deficits as perioperative neurocognitive disorders. They include confusion, delirium and longer-term problems with memory, concentration and attention. These changes can last for weeks or months after the surgery, often leading to longer hospital stays, loss of independence and even increased risk of death. Yet there are currently no proven drug treatments to prevent or reverse them. Our goals are to understand why these problems occur and determine how to stop them. To address this urgent need, we established the world's first Perioperative Brain Health Centre at Sunnybrook Health Sciences Centre, which brings cutting-edge research from the laboratory bench to the patient's bedside. Our research focuses on a "memory-blocking" protein, a subtype of GABAA receptors, in the brain. Normally, this protein helps regulate learning and memory. However, our preliminary studies have shown two harmful changes that occur in the brain after surgery. First, nerve cells make too many of these memory-blocking receptors, and second, certain support cells (called astrocytes) make and release excess amounts of the chemical messenger that activates the receptors. Together, this "double hit" depresses the brain's memory circuits, making it harder to think and remember. To uncover how surgery triggers these changes, we will study mice using a range of experimental approaches. We will also test whether existing or new drugs can restore healthy brain function. Our results are expected to guide future clinical studies in patients, with the ultimate goal of protecting brain health and preserving independence for older adults after surgery.