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Wearable sensor shows link between blood pressure and intracranial pressure

Publicado em 08 junho 2021

Brazilian researchers have simultaneously demonstrated the mechanism that links high blood pressure with increased intracranial pressure, validated a non-invasive method of monitoring intracranial pressure, and proposed a treatment for high blood pressure that does not affect intracranial hypertension.

The study was supported by FAPESP and involved a collaboration between researchers from São Paulo State University (UNESP) and Brain4care, a startup based in São Carlos. It could lead to novel treatments for intracranial hypertension and its complications, including stroke. The main results are reported in the journal Hypertension.

The researchers monitored blood pressure and intracranial pressure in rats for six weeks. “We wanted to investigate what happened to the intracranial pressure during the time when the animals became hypertensive. We were the first to succeed in monitoring this process non-invasively by tracking changes in the shape of the intracranial pressure curve. “

Our study suggests that if diagnosed early and treated with losartan, a drug commonly used by patients with high blood pressure, intracranial hypertension can be prevented. It blocks the effects of angiotensin II [a naturally occurring peptide that can cause vasoconstriction and an increase in blood pressure], which we also show is important to control intracranial pressure, “said Eduardo Colombari, lead researcher on the study. Colombari is a professor at the UNESP Dental School in Araraquara (FOAr).

Cerebral pressure typically increases due to a tumor, encephalitis, meningitis, aneurysm, or similar problems, but the researchers showed that chronic high blood pressure can also affect cerebral compliance, leading to increases in intracranial pressure.

In the study, researchers used vascular clips to simulate renal artery obstruction in rats, which restricted blood flow to a kidney. The reduced irrigation triggered the pressure-regulating renin-angiotensin system, causing the kidney to release peptides, enzymes and receptors that constrict blood vessels and increase blood pressure throughout the organism. In the third week of monitoring, when the rats were considered hypertensive, the blood pressure rose even more, which led to fluid retention and, above all, to an increase in cerebral blood flow.

“If the high blood pressure is not treated, the condition can get worse,” said Colombari. “The increase in intracranial pressure caused by systemic hypertension affects the brain’s ability to stabilize pressure [cerebral autoregulation]. This can also break the blood-brain barrier. Our study showed that the rats’ blood-brain barrier was weakened by the third week.

When the barrier is breached, substances and products of the renin-angiotensin system as well as inflammation-promoting substances present in the blood vessels can enter the interstitial space in which the neurons are located, especially in regions that are important for integrative neurohumoral adaptation, such as the heart -Circulatory system, respiratory and renal systems, among others. “

Treatment of intracranial hypertension

A disruption of the blood-brain barrier puts areas of the nervous system at risk that are important for the overall control of cardiovascular pressure. “How is intracranial hypertension treated now? By inducing a coma or administering a diuretic to break the fluid retention in the skull. These methods are relatively unspecific and highly systemic. A deeper understanding of the relationship between high blood pressure and intracranial hypertension points to the possibility of a new field of study in pharmacology, “said Gustavo Frigieri, Scientific Director of Brain4care.

Part of the study included a comparison between the intracranial pressure measured with the non-invasive sensor and that measured with the invasive method. The wearable sensor developed by Brain4care was used to measure intracranial pressure in patients with systemic impairments and has been licensed by the National Health Surveillance Agency (ANVISA) in Brazil and the Food and Drug Administration (FDA) in the USA.

Frigieri also sees many possible applications in basic research. “By comparing the non-invasive and invasive methods, we have validated our technology for use in scientific research with small animals,” he said. “Due to the aggressiveness of the conventional method, it can close open gaps, which carries a considerable risk of infection because a hole is drilled in the skull to insert a sensor.”

Blood circulation and hormones

At the end of the study, the researchers treated the animals with losartan, which lowered blood pressure and intracranial pressure. “It’s not a cause-and-effect relationship because when we lowered blood pressure with a vasodilator, brain pressure was not affected.” [hydralazine]. We observed a severe impairment of the brain and the angiotensin inhibitor [losartan] improved both blood pressure and cerebral blood flow, “said Colombari.

By the sixth week of the experiment, before any medication was administered, the blood pressure was high (190 per 100 mmHg) and the intracranial pressure had increased significantly. The researchers discovered changes in the waveforms of the intracranial pressure pulses. Each heartbeat (systolic or diastolic) pumps blood to the brain, creating the first peak (P1). A second wave (P2) correlates directly with intracranial artery volume and cerebral compliance, important factors observed immediately prior to ventricular diastole.

According to the researchers, the second wave is linked to the compliance of brain tissue and arterial elasticity in the skull, so the energy of the first wave is absorbed. However, disruption of the blood-brain barrier and loss of cerebral compliance impede control of P2, and the first wave becomes stronger than the second.

At this point we found that P2 is higher than P1, which is the opposite of the normal situation. This is due to the loss of protection provided by the blood-brain barrier, causing the brain to expand and fluid to leak into the interstitium. “

Eduardo Colombari, Study Director, São Paulo Research Foundation


Research Foundation São Paulo

Journal reference:

Fernandes, MV, et al. (2021) Intracranial pressure during the development of renovascular hypertension. Hypertension: Journal of the American Heart Association.