Coagulation

Blood substitution therapy rescues the brain from ischaemic damage


A novel strategy to prevent stroke related brain ischaemia has been suggested by US neuroscientists who found that blood replacement reduced infarctions and improved neurological deficits in animal models.

Researchers from West Virginia University (WVU) say blood replacement therapy may work by substantially decreasing brain antigens and inflammatory immune components of blood following a stroke.

In studies using mice models of stroke they showed that blood replacement therapy reduced cytokine storm in plasma by reducing and preventing infiltration of inflammatory neutrophils following a stroke.

The mechanism also appeared to involve a protease called MMP-9, which can lead to blood-brain barrier leakage and degeneration in brain tissue, they said in their article published in Nature Communications.

They said the mechanism could be explained by brain antigens being released through the blood brain barrier openings and may activate the immune system after stroke.

“Thus, the removal of blood from stroke mice may reduce the levels of brain antigens in circulating blood and alleviate the activation of immune system by brain antigens,” they wrote.

“Second, the removal of blood from stroke mice may diminish activated white blood cells and decrease many deleterious signals, such as cytokines, chemokines, proteases, and proteinases in circulating blood after stroke.”

“Third, as observed in patients with thrombotic thrombocytopenic purpura (TTP) disease, where the process of a blood transfusion may supply nutrition factors for the TTP patients, blood may also provide oxygen and many other neuroprotective factors for stroke brains,” said the researchers, led by Dr Sophie Ren, research assistant professor in the Department of Neuroscience and director of the WVU Experimental Stroke Core.

The animal model showed that replacing 20% of the blood in a mouse was enough to show a profound reduction in damage to the brain.

The study’s co-authors include Dr James Simpkins, director of the Center for Basic & Translational Stroke Research.

“The idea is to change the immune response that happens after stroke,” Dr  Simpkins said.

He said that neutrophils played a role in increasing the levels of an enzyme called MMP-9, which can lead to blood-brain barrier leakage and degeneration in brain tissue.

“The immune system doesn’t recognize much of what’s happening when there’s a stroke,” Dr Simpkins said. “So the neutrophils go to the brain and try to clean up the damage that happens. But there’s too much in the brain and those same neutrophils release MMP-9, which then exacerbates the damage.”

“What we learn is that stroke is simply not a cerebral vascular event. It’s a whole-body event. Both the brain and the body get signals that something’s going on in the brain and as the immune system responds to try to help, it actually worsens the outcome. Therefore, by removing the blood and replacing it with the blood of those that have not experienced stroke, we get good outcomes.”

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