Reservoir Neuroscience, Inc, has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, an $80,143 grant to study “Therapies to Protect the Blood-Brain Barrier After Surgery.” The project will evaluate the efficacy of Reservoir’s experimental compounds to protect the blood-brain barrier and prevent cognitive deficits and delirium-like behavior following orthopedic surgery. Designed as a pre-clinical academic-industry collaboration, this study has the potential to advance novel, first-in-kind treatments to improve debilitating patient outcomes in postoperative neurocognitive disorders (PND) – an unmet disease area.
Surgeries, including cardiac and orthopedic, often cause neurological complications, such as post-operative delirium and cognitive decline. These outcomes can be severely debilitating and in older adults, can create risk for onset of chronic dementia. It is not yet known how delirium and PNDs develop, or how to effectively treat this complication.
The Neuroinflammation and Cognitive Outcomes Laboratory at Duke Anesthesiology, directed by Terrando, has developed models to study the pathogenesis of postoperative delirium and strategies to combat it. In particular, the investigators have focused on the role for surgery-induced systemic inflammation in causing breakdown of the blood-brain barrier (BBB), a critical interface between the periphery and the central nervous system that regulates brain homeostasis to enable proper functioning. The BBB is often impaired in aging and neurologic disorders, such as epilepsy and Alzheimer’s disease. They have described changes in the BBB following orthopedic surgery, suggesting that opening of this barrier enables immune cells (like monocytes) and molecules (like fibrinogen) to access the brain and trigger pathological disease outcomes. This vascular pathology is especially evident in the context of neurodegeneration as they have described in a recent study published in Alzheimer’s and Dementia.
“The role of the blood-brain barrier in conditions like delirium is just starting to emerge. We are thrilled for this opportunity to work with Reservoir Neuroscience to test novel therapeutics that have the potential to heal the blood-brain barrier and hopefully prevent delirium,” says Terrando, associate professor in anesthesiology.
Reservoir Neuroscience, Inc, is developing new drugs to treat BBB dysfunction. These experiments are designed to provide proof-of-concept of a novel approach to improve outcomes in a rodent model of orthopedic surgery.