Researchers at Northwestern University Feinberg School of Medicine have identified in mice a previously1 unknown protective mechanism2 by which the smallest blood vessels4(血管) remove blood clots5(血凝块,血栓) and other blockages7 from the brain. The findings provide insights into mechanisms8 that may be involved in age-related cognitive9(认知的,认识的) decline, Alzheimer's disease and recovery from stroke. These findings were described in the May 27 issue of Nature by Jaime Grutzendler, M.D., and colleagues. The study was supported by the National Institute on Aging (NIA), part of the National Institutes of Health.
Uninterrupted blood flow is critical for brain function, and the brain has developed various mechanisms to maintain it. Blockages(堵塞,妨碍) in the smallest blood vessels can be cleared by processes that disintegrate10(破碎,瓦解) or wash them out. However, not all blockages are cleared completely. Persistent11 blockage6 can reduce or stop blood flow, limiting the supply of oxygen and nutrients12 to the surrounding tissue and nerve cells. This, in turn, can lead to impaired13(受损的) communications between nerve cells and ultimately cell death.
The researchers used a newly developed imaging technique that can view the smallest blood vessels, known as microvessels(微脉管) , in the brains of living mice. They found that two to seven days after a blockage in brain microvessels, the cells lining14 the blood vessel3 wall engulf15(吞没) the remaining portion of the blockage, encapsulate(压缩,封装) it, seal it off from the interior of the blood vessel and finally expel the blocking material outside of the vessel. As a result of this process, blood flow is restored to the affected16 area.
"These are intriguing17(米人的,有趣的) findings," said NIA Director Richard J. Hodes, M.D. "They open new avenues of basic research that may increase our understanding of how microvessels are maintained in the brain and throughout the body."
The research team demonstrated that this complex protective mechanism involves the activity of an enzyme18(酶) , matrix metalloprotease 2/9, which breaks down large proteins and is known to play a role in blood vessel development and in stroke.
The researchers also found that the ability to move the blockage out of the blood vessel diminished(减少,削弱) with age. Young mice (age 4 months) were able to clear blockages more quickly and thoroughly19 than older mice (age 22 months). The incomplete removal of blockages in the brains of older mice led to a prolonged(延长的,拖延的) shortage of oxygen to the surrounding nerve cells and damaged the connections between nerve cells in the vicinity of(在……附近) the obstructed20 blood vessels.
"The reduced efficiency of this protective mechanism in the older brain and its effect on the function of nerve cells in the brain may significantly contribute to age-related cognitive decline," said Suzana Petanceska, Ph.D., of the Neurobiology of Aging Branch in NIA's Division of Neuroscience, which funded the research. "This may also be part of the mechanism by which vascular21(血管的) risk factors such as high blood pressure and diabetes22(糖尿病) increase the risk of Alzheimer's disease with age."