Sticky Situation Inside Blood Vessels Can Worsen Stroke Damage
martyb writes:
Sticky situation inside blood vessels can worsen stroke damage:
A stroke appears to create a sticky situation inside the blood vessels of the brain that can worsen damage days, even months later, scientists report.
They have found that after stroke, exosomes - nanosized biological suitcases packed with an assortment of cargo that cells swap, like proteins and fats - traveling in the blood get activated and sticky and start accumulating on the lining of blood vessels, according to a collaborative study by the Medical College of Georgia and the University of Oxford.
Like a catastrophic freeway pileup, platelets, also tiny cells that enable our blood to clot after an injury, start adhering to the now-sticky exosomes, causing a buildup that can effectively form another clot, further obstruct blood flow to the brain and cause additional destruction, they report in the journal Scientific Reports.
One thing traveling exosomes typically aren't is sticky rather, much like our real suitcases, they have a smooth label that marks their intended destination, says Dr. Zsolt Bagi, vascular biologist in the MCGDepartment of Physiology. He and Dr. Daniel C. Anthony, professor of experimental neuropathology/pharmacology in the Department of Pharmacology at the University of Oxford, are co-corresponding authors of the new study.
But when these external destination tags become inexplicably sticky following a stroke, not only do exosomes not reach their destination, they can worsen stroke outcome, he notes.
In a bit of a perfect storm, the scientists have shown in both stroke models and human blood vessels that exosomes cruising through the blood then pick up RGD, the unique and normally sticky peptide sequence, arginine-glycine-aspartate, which is key to the pileup that can cause additional brain damage.
More typically, exosomes carry a negligible amount of RGD, a protein that's important in holding together the extracellular matrix that helps cells connect and form tissue. In the aftermath of a stroke, cells and the extracellular matrix both get damaged, and sticky RGD is effectively set free.
Platelets normally aren't exposed to RGD, which should mostly be sequestered in the extracellular matrix, so they become angry, activated and also sticky in response. "There is always a problem when platelets become activated," Bagi says.
Journal Reference:
Zsolt Bagi, Yvonne Couch, Zuzana Broskova, Francisco Perez-Balderas, Tianrong Yeo, Simon Davis, Roman Fischer, Nicola R. Sibson, Benjamin G. Davis, Daniel C. Anthony. Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-019-52127-3
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