Within the mind cortex of mice (left) with out hypertension, few endothelial cells (yellow) present growing old or senescence (blue). After angiotensin is run, which causes hypertension (center), many extra endothelial cells (blue) with growing old and harm are current within the cortex. Blocking angiotensin receptors (proper) rescues endothelial cells. Credit score: Dr. Anthony Pacholko
Hypertension impairs blood vessels, neurons and white matter within the mind nicely earlier than the situation causes a measurable rise in blood stress, in line with a brand new preclinical examine from Weill Cornell Medication investigators. The modifications assist clarify why hypertension is a significant danger issue for growing cognitive problems, resembling vascular cognitive impairment and Alzheimer’s illness.
The preclinical findings, printed Nov. 14 in Neuron, reveal that hypertension might induce early gene expression modifications in particular person mind cells that would intrude with considering and reminiscence. The findings might result in drugs that each cut back blood stress and stop cognitive decline.
Sufferers with hypertension have a 1.2 to 1.5-fold larger danger of growing cognitive problems than folks with out the situation, however precisely why is just not understood. Whereas many present hypertension drugs efficiently decrease hypertension, they usually present little or no impact on mind operate. This means blood vessel modifications might trigger harm independently of the elevated stress related to hypertension.
“We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice—before blood pressure increased,” mentioned senior writer Dr. Costantino Iadecola, director of the Feil Household Mind and Thoughts Analysis Institute, professor of neuroscience and Anne Parrish Titzell Professor of Neurology at Weill Cornell. “The bottom line is something beyond the dysregulation of blood pressure is involved.”
Dr. Anthony Pacholko, postdoctoral affiliate in neuroscience at Weill Cornell, co-led the work.
Growing old too quickly
In earlier work, Dr. Iadecola’s crew discovered that hypertension impacts the operate of neurons globally, however latest improvements in single-cell applied sciences have allowed them to zero in on what is occurring within the several types of cells within the mind on the molecular stage.
To induce hypertension in mice, the researchers administered the hormone angiotensin, which raises blood stress, mimicking what occurs in people. Then, they checked out how several types of mind cells had been impacted three days later (earlier than blood stress elevated) and after 42 days (when blood stress was excessive, and cognition was affected).
Graphical summary. Credit score: Neuron (2025). DOI: 10.1016/j.neuron.2025.10.018
At day three, gene expression dramatically modified in three cell varieties: endothelial cells, interneurons and oligodendrocytes. Endothelial cells, which line the inner floor of blood vessels, aged prematurely with decrease vitality metabolism and better senescence markers.
The researchers additionally noticed early indicators of a weakened blood-brain barrier, which regulates the inflow of vitamins into the mind and retains out dangerous molecules. Interneurons, mind cells that regulate the stability of excitatory and inhibitory nerve indicators, had been broken, resulting in an imbalance between inhibition and excitation like that seen in Alzheimer’s illness.
As well as, oligodendrocytes that enrobe nerve fibers with myelin didn’t correctly specific genes liable for their upkeep and alternative. With out sufficient oligodendrocytes to keep up the well being of the myelin sheath, neurons finally lose the power to speak with one another, which is important for cognitive operate. Much more gene expression modifications had been noticed at day 42, coinciding with cognitive decline.
“The extent of the early alterations induced by hypertension was quite surprising,” Dr. Pacholko mentioned. “Understanding how hypertension affects the brain at the cellular and molecular levels during the earliest stages of the disease may provide clues to finding ways that can potentially block neurodegeneration.”
Shifting ahead
An antihypertensive drug already in medical use known as losartan inhibits the angiotensin receptor. “In some human studies, the data suggest that the angiotensin receptor inhibitors may be more beneficial to cognitive health than other drugs that lower blood pressure,” Dr. Iadecola mentioned. In further experiments, losartan reversed the early results of hypertension on endothelial cells and interneurons within the mouse mannequin.
“Hypertension is a leading cause of damage to the heart and the kidneys, that can be prevented by antihypertensive drugs. So independent of cognitive function, treating high blood pressure is a priority,” Dr. Iadecola mentioned.
Dr. Iadecola and his crew at the moment are investigating how the untimely growing old of small blood vessels induced by hypertension might set off interneuron and oligodendrocyte defects. And in due time, the researchers hope to uncover one of the best ways to stop or reverse the devastating results of hypertension on cognitive operate.
Extra info:
Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Decision, Neuron (2025). DOI: 10.1016/j.neuron.2025.10.018. www.cell.com/neuron/fulltext/S0896-6273(25)00799-8
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Hypertension impacts the mind a lot sooner than anticipated, examine suggests (2025, November 14)
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