High blood pressure (hypertension) can lead to a decline in cognitive functions and significantly increase the risk of dementia. Certain cells of the immune system apparently play a crucial role in this connection, which could also open up new therapy options.
A research team led by Dr. Costantino Iadecola from the Feil Family Brain and Mind Research Institute (USA) and Dr. Monica M. Santisteban from Vanderbilt University Medical Center used mice to investigate the mechanisms through which the connection between high blood pressure and dementia is mediated. The results are in the specialist magazine “Nature Neuroscience”.
High blood pressure and dementia
More than a billion people worldwide are affected by high blood pressure and it is one of the main causes of cognitive impairment, the researchers report. For example, a previous study had already shown that high blood pressure weakens cognitive performance.
Various research studies have also shown that lowering blood pressure can help prevent dementia and that poorly controlled high blood pressure causes damage to the brain. However, the mechanisms by which hypertension is linked to the decline in cognitive functions have remained largely unclear.
Influence of interleukin-17
In studies on mice, experts have now been able to demonstrate that neurovascular and cognitive dysfunction in high blood pressure depends on interleukin (IL)-17, a cytokine that is elevated in people with high blood pressure.
Normally, Il-17 is released in the body to activate the immune system in the brain and spinal fluid, the researchers explain. IL-17 activates certain immune cells in the brain, the so-called macrophages.
Activated brain macrophages
A series of experiments confirmed that these macrophages are important for the observed decline in cognition, the team reports.
In mice that lacked the receptor for IL-17 in brain macrophages, as well as in mice whose brain macrophages were exhausted, no effects of high blood pressure on cognitive abilities were detectable – despite other symptoms of hypertension.
The researchers initially suspected that IL-17 is released in the intestine and then travels through the bloodstream to the brain, where it impairs the ability of the blood vessels to respond appropriately to increased brain activity.
But blocking the ability of the brain’s blood vessels to respond to IL-17 only partially reversed the cognitive impairment. IL-17 apparently also influences the brain via another pathway.
A clue came from other recent studies that suggested that a layer of the brain’s protective covering, known as the dura mater, contains certain immune system cells (T cells) that secrete IL-17 and can influence the behavior of mice, report the researchers.
IL-17 increased in the dura mater
Using special mice in which the cells glow fluorescent green when they produce IL-17, they were able to demonstrate that in high blood pressure, IL-17 is increased in the dura mater and is then released into the tissue.
In addition, the protective coverings of the brain, the so-called meninges, which prevent unwanted penetration into the brain, were disrupted in the mice with experimentally induced high blood pressure, which allowed IL-17 to enter the cerebrospinal fluid, the experts report.
The influence of T cells in the dura mater was also confirmed in further experiments. According to the researchers, for example, antibodies that block the activity of T cells in the meninges were able to reverse the cognitive losses in the mice with high blood pressure.
Two possible mechanisms
Overall, the study results suggest that high blood pressure can affect cognitive function through two pathways. One of these is IL-17, which affects blood vessels, the researchers explain. Here, however, the influence seems relatively small.
“A more pronounced, central effect is caused by cells in the meninges releasing IL-17, which directly affects immune cells in the brain. It is these immune cells that are activated by signals from the meninges and ultimately influence the brain in a way that leads to cognitive impairment,” explains Dr. Iadecola.
Hope for new therapies
According to the researchers, the experiments carried out also suggest that the targeted treatment of overactive T cells could be a new treatment approach to counteract the effects of high blood pressure on cognition and reduce the risk of dementia. This now needs to be investigated in further studies. (fp)