Research led by the University of Vermont shines a light on the mechanism behind vascular dementia in a mouse model, which the investigators hope will lead to better treatments being developed for the neurodegenerative condition.
As reported in the journal PNAS, reduced blood flow to the brain is known to be a key factor in the hypertension-induced vascular dementia disease process, but the mechanism behind this was unclear, making it difficult to design therapies to improve blood flow.
The current study investigated this mechanism in model mice and found the reduced cerebral blood flow was caused by a part of the smooth muscle cells becoming separated from the plasma membrane leading to a breakdown in cell signaling that would lead to the blood vessels relaxing under normal circumstances.
Around 14 percent of Americans aged 71 years or older have some form of dementia and about 20 percent of these are vascular dementia cases. Vascular dementia can be triggered by different causes, but one key driving factor is high blood pressure.
“Vascular dementia is one of the most devastating sequelae of hypertension. Progressive small vessel disease of the brain results in characteristic radiological changes, including white matter hyperintensities, enlarged perivascular spaces, and cerebral atrophy,” write the authors.
To try and understand the mechanism behind hypertension-triggered vascular dementia better, Mark Nelson, a professor at the University of Vermont, and colleagues at the University of Manchester in the U.K. used a mouse model (BPH/2) of hypertension and vascular dementia to study the physiological mechanism behind the condition. The mice have reduced cerebral blood flow, highly constricted pial arteries, and similar behavioral traits to those seen in human vascular dementia.
Using a combination of techniques, the team found that the arteries in the brains of the mice were constricted, because a part of the smooth muscle cell known as the sarcoplasmic reticulum had separated from the plasma membrane. This separation stopped calcium signals that would normally trigger relaxation of the blood vessels from reaching their potassium channel targets.
“By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks,” said Adam Greenstein, a professor and clinician scientist at the University of Manchester and one of the leaders of the research, in a press statement.
“Any drugs that are discovered to improve brain blood supply may also be able to open a new line of attack in treating Alzheimer’s disease, which causes very similar damage to blood vessels as vascular dementia. Drugs to restore healthy blood flow could make current treatments, which focus on removing harmful amyloid plaques in the brain, more effective.”