Researchers have discovered how blood vessels protect the brain during inflammation--a finding that could lead to the development of new treatments for neurodegenerative diseases such as stroke, epilepsy and multiple sclerosis.
In a study published in the Proceedings of the National Academy of Sciences, the researchers describe how podocalyxin, a protein in blood vessels, plays a key role in preventing harmful blood components from leaking into the brain during inflammation in response to infection or injury.
The discovery marks the first time scientists have understood the function of podocalyxin in the blood-brain barrier--a membrane that separates the brain from blood circulating in the rest of the body and that is essential for maintaining healthy brain function. Disruption of this barrier is common in neurodegenerative diseases and contributes to disease symptoms.
To conduct the study, the researchers performed an analysis of the effects of podocalyxin loss in human endothelial cells, as well as in mouse models of inflammation. They were able to show that endothelial cells, which provide the inner tubing of blood vessels, require podocalyxin to strengthen blood vessels. The protein helps generate tight contacts between the cells so that potentially harmful blood components or bacterial and viral toxins can't permeate brain tissue during times of inflammation.
In the absence of podocalyxin, endothelial cells lack adherens junctions and focal adhesions and display a disorganized cortical actin cytoskeleton. Thus, Podxl has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers.
"Until now, the function of this protein was a mystery," said the co-lead author. "Nobody thought to look at this as something controlling the blood-brain barrier."
The researchers hope their findings will lead to the development of new drugs and treatments for preventing blood-brain barrier breakdown. They have also started manipulating podocalyxin to control opening the blood-brain barrier.
"A significant hindrance to treating neurodegenerative diseases at the moment is that most drugs can't cross the blood-brain barrier," said the study's senior author. "But if we are able to induce transient opening of the blood-brain barrier, that could allow us to deliver treatment directly to brain tissue."
How blood vessels protect the brain during inflammation
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