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Excessive calcium contributes to harmful inflammation in ischemic stroke, and targeting it may provide doctors with a new way to improve patient outcomes, new research from the University of Virginia School of Medicine suggests.
Petr Tvrdik, PhD, found that immune cells called microglia are flooded with calcium waves in the wake of ischemic strokes, which are strokes caused by a disruption in blood flow to the brain. These calcium waves, he determined, trigger harmful inflammation that can worsen the effects of stroke.
Blocking the calcium waves, his work suggests, can help control harmful inflammation and offer doctors a way to reduce the often debilitating effects of ischemic stroke.
“This publication culminates several years of research into this previously unrecognized aspect of stroke pathology,” said Tvrdik, of UVA’s Departments of Neurosurgery and Neuroscience. “Our success would not be possible without the exceptional contributions of the study’s lead authors, medical students Kathryn Kearns and Lei Liu. Special mention in this regard goes to the support of Medical Summer Research Projects, headed by Dr. Driscoll, who has provided a stimulating environment for students and much needed help for my lab. “
The answer is football
Scientists have known for nearly two decades that lack of blood flow to the brain during ischemic strokes results in surges of abnormal brain activity, which are called cortical spreading depolarizations or CSDs. These CSDs are harmful and can set the stage for further brain damage. In addition to occurring in ischemic stroke, they are also seen in traumatic brain injury (TBI), migraine, and subarachnoid hemorrhages, which are bleeding into the space between the brain and its surrounding membrane.
New research by Tvrdik and his colleagues sheds light on what is happening during these CSDs. Working on lab mice, the scientists found that ischemic strokes trigger waves of calcium that flood the brain’s defenders, the immune cells known as microglia. This calcium overload “triggers CSDs in a recurrent and progressive way,” the researchers write in a new scientific paper.
“More research is needed to determine how harmful these calcium waves are,” Tvrdik said. “Our article received 5% social media attention. We hope this enthusiasm in the field translates into more funding for our research.”
It is promising that the researchers were able to use a drug to reduce calcium waves in their mouse models by more than 25%. This gives them hope that a similar approach can be used to reduce the damaging effects of calcium waves in stroke patients, although more research is needed.
“We are fortunate to partner with CalciMedica, a pharmaceutical company specializing in the development of drugs that suppress calcium overload in immune cells,” Tvrdik said. “We share the vision that our research could help identify an effective drug that will improve the recovery of stroke survivors.”
Reference: Liu L, Kearns KN, Eli I, et al. Microglia calcium waves during the hyperacute phase of ischemic stroke. Stroke. 2020. doi: 10.1161 / STROKEAHA.120.032766
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