Healthcare (Commonwealth Union) – Hypertension remains a serious health concern across the globe.
A recent preclinical study from Weill Cornell Medicine researchers shows that hypertension can damage blood vessels, neurons, and white matter in the brain long before blood pressure rises to detectable levels. These early changes may help explain why high blood pressure is a significant risk factor for cognitive conditions like vascular cognitive impairment and Alzheimer’s disease.
Published on Nov. 14 in Neuron, the study indicates that hypertension may trigger early shifts in gene activity within individual brain cells, potentially affecting memory and thinking. These insights could pave the way for treatments that not only lower blood pressure but also protect cognitive function.
People with hypertension face a 1.2 to 1.5 times greater risk of developing cognitive disorders compared with those without high blood pressure, though the underlying reasons remain unclear. While many existing hypertension medications effectively reduce blood pressure, they often have minimal impact on brain health, suggesting that changes in blood vessels may independently contribute to cognitive damage.
“We found that the major cells responsible for cognitive impairment were affected just three days after inducing hypertension in mice—before blood pressure increased,” explained the senior author Dr. Costantino Iadecola, who is director of the Feil Family Brain and Mind Research Institute and professor of neuroscience and Anne Parrish Titzell who is Professor of Neurology at Weill Cornell Medicine. “The bottom line is something beyond the dysregulation of blood pressure is involved.” The co-lead of the research was Dr. Anthony Pacholko, postdoctoral associate in neuroscience at Weill Cornell.
In earlier studies, Dr. Iadecola’s group demonstrated that hypertension disrupts neuronal function across the brain. However, recent advances in single-cell technologies, a technique that can analyze biological data have enabled the team to investigate how distinct brain cell types are affected at the molecular level.
To model hypertension in mice, the researchers administered the hormone angiotensin, which elevates blood pressure, replicating the process seen in humans. They then examined the impact on various brain cell types both three days later—before any rise in blood pressure—and after 42 days, when hypertension was established and cognitive deficits had emerged.
In the third day gene expression had been changed significantly in three cell populations: endothelial cells, interneurons, and oligodendrocytes. Endothelial cells, which are lined on the blood vessels, demonstrated signs of premature aging, reduced energy metabolism, and cellular senescence, suggesting they had halted division. The researchers also noted early indications of a compromised blood-brain barrier, that is generally responsible for controlling nutrient entry guarding the brain from harmful substances.
Interneurons—cells that modulate signals between motor and sensory neurons—were also impaired, resulting in an imbalance between excitatory and inhibitory signaling similar to patterns observed in Alzheimer’s disease. Meanwhile, oligodendrocytes, which wrap neurons in myelin, exhibited disrupted gene activity necessary for their maintenance and replacement. A shortage of functional oligodendrocytes can compromise myelin integrity, preventing neurons from communicating effectively, a process essential for cognition.
In the forty second day, these gene expression changes were even more pronounced, coinciding with measurable cognitive decrease for the hypertensive mice.
Dr. Pacholko indicated that the extent of the early changes brought about by hypertension was quite astonishing.
He further pointed out that knowing the way hypertension impacts the brain at the cellular and molecular levels during the earliest stages of the disease could possibly help in forming therapeutic strategies in halting the progression of neurodegeneration for individuals with hypertension.
An existing anti-hypertensive medication, losartan, works by blocking the angiotensin receptor. Dr. Iadecola indicated that certain human studies have noted that angiotensin receptor blockers might offer greater benefits for cognitive health compared with other blood pressure–lowering drugs. Further experiments showed that losartan could reverse the initial impact of hypertension on endothelial cells and interneurons in mice.
