In a major advance in brain health, scientists have demonstrated for the first time how faulty interactions between aging red blood cells and narrow capillaries can lead to bleeding. Until now, the cause of this serious condition has been brain hemorrhage caused by injured or damaged blood vessels. "It has been thought that for cerebral hemorrhage to occur, blood vessels must be damaged or destroyed. We found that increased interaction of red blood cells with brain capillaries represents another source of development," said co-corresponding author Xiangmin Xu, a professor at the University of California, Irvine (UCI).
The team identified how aging red blood cells "get stuck" in the brain's narrow capillary network, causing microbleeds at the site. Microbleeds in the brain in older adults are associated with a higher risk of Alzheimer's disease, high blood pressure and ischemic stroke.
Capillaries, the smallest blood vessels in the body, use an ingenious membrane mechanism to drain blockages, but this mechanism begins to decline as we age.
A 2010 study identifying this mechanism also found that in the aging brain, it slows down by 30 to 50 percent and causes more capillaries to die.
The team used tert-butyl hydroperoxide to cause oxidative stress on red blood cells, then labeled the cells with a fluorescent tag and injected them into the brains of mice. Using two different methods, they saw that red blood cells got stuck in capillaries and were then cleared through a process called endothelial erythrophagocytosis. But when the cells moved out, microglia engulfed them, causing brain hemorrhages.
"We have explored this issue before in cell culture systems, but our current study is significant in expanding our understanding of the mechanisms by which small cerebral hemorrhages develop," said co-corresponding author Mark Fisher, a professor at the UCLA School of Medicine. "Our findings could have far-reaching clinical implications because we discovered a link between red blood cell damage and cerebral hemorrhage, which occurs at the capillary level."
The team says the discovery provides new avenues of research and potential treatments to help the aging brain maintain capillary function and prevent these aging cells from stalling on this important transport route.
"We need to study in detail the regulation of capillary clearance in the brain and analyze how this process relates to insufficient blood supply and ischemic stroke, the most common form of stroke, to help advance the development of targeted therapies," Fisher added.
The research was published in the Journal of Neuroinflammation.