A study in rats questions long-standing views on hypertension and suggests the brain may serve as a new target for treatment.
A recent study shows that consuming a diet high in salt causes inflammation in the brain, which in turn raises blood pressure.
The work, led by McGill University scientist Masha Prager-Khoutorsky in partnership with an interdisciplinary team from McGill and the Research Institute of the McGill University Health Centre, indicates that the brain may play a previously overlooked role in some forms of hypertension, a condition long thought to originate mainly in the kidneys.
“This is new evidence that high blood pressure can originate in the brain, opening the door for developing treatments that act on the brain,” said Prager-Khoutorsky, associate professor in McGill’s Department of Physiology.
Widespread impact of hypertension
Hypertension affects nearly two-thirds of adults over the age of 60 and is responsible for an estimated 10 million deaths globally each year. Because it often develops without obvious symptoms, the condition significantly raises the risk of stroke, heart disease, and other life-threatening complications.
A 3D reconstruction of a brain immune cell (purple) engulfing fragments of other brain cells (green and orange) after a high-salt diet. The images were captured using super-resolution microscopy and reconstructed with IMARIS software. Credit: Prager-Khoutorsky Lab
Roughly one-third of patients do not respond to standard treatments, which mainly target blood vessels and kidneys under the long-standing assumption that hypertension originates in those organs. Findings from the study, published in Neuron, indicate that the brain may also play a central role in driving the disease, especially in cases that are resistant to current therapies.
How salt disrupts the brain
To mimic human eating patterns, rats were given water containing two per cent salt, comparable to a daily diet high in fast food and items like bacon, instant noodles and processed cheese.
The high-salt diet activated immune cells in a specific brain region, causing inflammation and a surge in the hormone vasopressin, which raises blood pressure. Researchers tracked these changes using cutting-edge brain imaging and lab techniques that only recently became available.
“The brain’s role in hypertension has largely been overlooked, in part because it’s harder to study,” Prager-Khoutorsky said. “But with new techniques, we’re able to see these changes in action.”
The researchers used rats instead of the more commonly studied mice because rats regulate salt and water more like humans. That makes the findings more likely to apply to people, noted Prager-Khoutorsky.
Next, the scientists plan to study whether similar processes are involved in other forms of hypertension.
Reference: “Microglia regulate neuronal activity via structural remodeling of astrocytes” by Ning Gu, Olena Makashova, Celeste Laporte, Chris Qilongyue Chen, Banruo Li, Pierre-Marie Chevillard, Graham Lean, Jieyi Yang, Calvin Wong, Jonathan Fan, Behrang Sharif, Susana Puche Saud, Misha Hubacek, Katrina Y. Choe, Margaret M. McCarthy, Arkady Khoutorsky, Charles W. Bourque and Masha Prager-Khoutorsky, 19 August 2025, Neuron.
DOI: 10.1016/j.neuron.2025.07.024
Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Azrieli Foundation
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