Blood Replacement Rescues Mice from Stroke Damage

Researchers have partially mitigated the effects of an ischemic stroke in mice simply by replacing a small amount of their blood with that of a healthy donor. Days after receiving the transplant, mice had less tissue damage surrounding the clot and suffered fewer neurological side effects compared to mice that had not received a blood infusion.
The results, published August 25 in Nature Communications, highlight the link between strokes in the brain and the immune system. At least some of the damage caused by strokes, the authors say, is the result of an overreactive immune response during which cells sent to an injury to fight infection and facilitate repair instead harm sensitive brain tissue.
“The initial impetus for the study was to determine the extent to which this immune response, which we know is very rapid and very profound, contributes to brain damage from stroke,” James Simpkins, a neuroscientist at West Virginia University and a coauthor of the paper, tells The Scientist.
In the moments following a stroke, the body activates a complex immunological response, funneling messenger molecules past the blood-brain barrier and into the blood to recruit immune cells to the damaged area. Neutrophils—white blood cells that are often the first to arrive—increase the levels of an enzyme called MMP-9 that degrades the blood-brain barrier further, the better to allow more immune cells and signaling molecules to pass through. In some instances, the body can release too many of these molecules, such as cytokines, into the blood at once, and the resulting cytokine storm can damage brain tissue surrounding a clot, causing inflammation and degeneration of brain tissue.
To better understand the immunological link between brain and blood, the researchers used a mouse model to mimic an ischemic stroke that was subsequently cleared by the scientists after 90 minutes. Between six and seven hours after the stroke, the mice received a blood transfusion of either 250 or 500 microliters of blood from a healthy donor, roughly 10 percent to 20 percent of a mouse’s total blood volume, after the same volume had been removed from the animal. One hour later, the scientists tested the permeability of the blood-brain barrier, followed by a measure of the amount of damaged brain tissue 24 hours after treatment.
Mice that received blood replacements suffered fewer ill effects than control mice, with the benefits being strongest in the group receiving a larger volume of new blood. The extent of tissue damage surrounding the clot decreased by as much as 70 percent to 80 percent, and cognitive defects brought on by the stroke improved in treated mice. Both the decrease in tissue damage and the rescuing of neurological deficits persisted for at least three days after the initial stroke.
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