Research Study: Mechanisms of Neurocognitive Decline After Subarachnoid Hemorrhage
Primary Investigator: David Y. Chung, M.D., Ph.D., Instructor in Neurology at Harvard Medical School, Division of Neurocritical Care and Emergency Neurology at Massachusetts General Hospital
Background: Subarachnoid hemorrhage (SAH) from a ruptured brain aneurysm is a life-altering condition that affects more than 30,000 Americans and costs $5.6 billion annually. Approximately 20% of patients who survive the initial rupture will go on to have subsequent, secondary brain injury. Furthermore, even patients with relatively good outcomes frequently suffer from persistent cognitive deficits precluding return to work. Both the pathophysiology underlying secondary brain injury and the mechanisms underlying lasting cognitive deficits remain unknown.
Emerging human evidence suggests that cognitive deficits following SAH are associated with altered functional brain connectivity. Moreover, there is strong human evidence that spreading depolarizations (SD)—similar to the phenomenon of spreading depression in migraine aura—are associated with secondary injury and cognitive decline after
SAH7-13. SDs are thought to arise out of ischemia14, but it is difficult to distinguish the individual contributions of SDs and ischemia to outcome using existing animal models. Therefore, we will use novel mouse models of SAH to examine the contribution of SDs in the absence of ischemia on functional brain connectivity and neurocognitive decline.
Research Objective: The goal of Dr. Chung's research is to prevent further brain damage after aneurysm rupture and to develop therapies that help survivors recover back to their baseline function. In particular, he is trying to understand why some patients who look well after surgical repair of an aneurysm go on to develop a poorly understood syndrome of progressive brain injury and functional decline. At the same time, he is trying to understand why others who do well after their hospitalization have long-lasting cognitive problems that prevent return to work.
Dr. Chung believes that a phenomenon called spreading depolarization causes further injury after aneurysm rupture by changing how different parts of the brain connect to each other. To study spreading depolarizations and connectivity, he has developed a set of non-invasive tools to experimentally cause spreading depolarizations in an animal model of aneurysm rupture. Furthermore, he has developed ways to determine how difference parts of the brain connect to each other using a cutting edge technique in living mice called resting state optical intrinsic signal imaging.
Outcomes: With funds from The Aneurysm and AVM Foundation, Dr. Chung believes that the findings from his research will be important for understanding why survivors of aneurysm rupture continue to develop brain injury in the hospital and suffer persistent long term cognitive deficits. The greatest hope is that knowledge gained from his work will lead to a breakthrough in the field and directly lead to new therapies for people who have had a ruptured brain aneurysm.
Source: David Y. Chung, M.D., Ph.D., Massachusetts General Hospital and Harvard Medical School . This research summary has been adapted and edited from Dr. Chung's research proposal.
