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Adjusting Neutrophil Behavior to Enhance Stroke Recovery

An emerging theme in regenerative research is the importance of the innate immune system to the mechanisms of tissue maintenance, and researchers have so far found a number of ways in which the behavior of these immune cells might potentially be adjusted in order to enhance healing. The scientific community has made initial strides with macrophages and microglia, shifting the balance of pro-inflammatory versus pro-regenerative cells, and here some of the same high level themes are observed in the response to injury of the innate immune cells known as neutrophils. It matters greatly as to whether these immune cells turn up at the point of injury in the mode of defending against intruding pathogens, or in the mode of assisting with repair; they are capable of both, but individual cells tend to be focused only on one of these at a given time.

White blood cells called neutrophils are like soldiers in your body that form in the bone marrow and at the first sign of microbial attack, head for the site of injury just as fast as they can to neutralize invading bacteria or fungi using an armament of chemical weapons. But when that injury is an intracerebral hemorrhage, which releases blood into the brain, neutrophils arrive at the point of battle only to discover that there's no infection to attack. Unless immediately removed from the brain by other immune cells, they actually cause damage and deploy an array of toxic chemicals into the brain that worsen injury.

Now researchers have discovered a way to temporarily suppress these soldiers' pro-killing effect and turn them into beneficial weapons that scavenge for toxins, potentially opening a door for a therapeutic approach to hemorrhagic stroke treatment. A hemorrhagic stroke occurs when an artery inside the brain leaks or ruptures. It is the second-most common form of stroke after ischemic stroke, has a 30 to 67 percent mortality rate and is the main cause of disabilities among adults. Because half of hemorrhagic stroke victims die within the first two days, researchers believe that deadly secondary damage, including through toxicity of iron from the breakdown of red blood cells, leads to an excess in free radicals and inflammation.

Along with carrying chemicals that could aggravate injury, neutrophils produce and release potentially beneficial molecules including lactoferrin, an iron-binding protein. At the same time the neutrophils are getting ready to attack inside the brain, the brain and spleen are releasing interleukin-27 molecules, which can signal to the neutrophils to produce more lactoferrin and thus benefit the brain as it recovers from the stroke injury. "This is one of the first discoveries showing that you can train neutrophils to act as friendly cells. We've adapted how the body already responds naturally, but it can take 12 to 18 hours for the signal to turn them from damaging neutrophils to the beneficial cells that release lactoferrin and by then, it can be too late. Treatment with lactoferrin in our models is effective in reducing brain damage after hemorrhage and we are working on a modified form of lactoferrin that could penetrate the brain better and quicker."

Link: https://www.uth.edu/media/story.htm?id=caf2ac24-bf5a-433e-aa00-e0d22ba0209b

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