Researchers have discovered that stabilizing dysfunctional endothelial cells with approved drugs reverses cellular dysfunction in a rat model of cerebral small vessel disease (SVD), hinting towards a new therapeutic approach for the treatment of vascular dementia. As life expectancies climb around the world and society ages, dementia - a group of symptoms characterized by declining memory and cognitive ability - has become a chief concern for scientists and caretakers. One of the most common causes of vascular dementia in the elderly is SVD, which occurs when small blood vessels in the brain are unable to nourish white matter tissue. SVD also contributes to the symptoms of Alzheimer's disease and triples the risk of stroke, rendering it a major cause of cognitive disability in the elderly. However, there are still no dependable therapies for the condition, partially due to a lack of understanding of the mechanisms underlying the changes in blood vessels. Here, Rikesh Rajani and colleagues zeroed in on the role of endothelial cells (ECs), which help prevent unwanted substances and cells from entering the brain. The research team studied brains from humans with SVD and observed they harbored dysfunctional ECs, and found a mutation that could be responsible for the dysfunction. Further analysis showed these ECs secreted a protein called HSP90α that impaired proper functioning of isolated connective tissue cells found in the brain. Approved drugs that stabilize ECs such as simvastatin (a cholesterol-lowering medication) reversed abnormalities in a rat model of SVD after seven weeks of treatment. The authors say that future studies should assess whether EC dysfunction can be reversed at a later stage of SVD, as well as test their findings in other animal models.
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Journal
Science Translational Medicine