Investigating the hypotensive effect of focused ultrasound neuromodulation and barbiturate-loaded nanodroplets in healthy and hypertensive rats.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Brain Stimulation Pub Date : 2024-11-01 Epub Date: 2024-12-04 DOI:10.1016/j.brs.2024.12.002

Harriet Lea-Banks, Neha Chauhan, Kullervo Hynynen

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引用次数: 0

Abstract

Background: Current strategies for reducing blood pressure (BP) are ineffective and unsafe for many patient populations, including drug-resistant hypertension and during pregnancy. Stimulating the periaqueductal grey (PAG) region has shown promise in treating drug-resistant hypertension in patients using deep brain stimulation.

Objective: To develop a minimally invasive neuromodulation technique for the sustained treatment of hypertension.

Methods: We have investigated BP reduction using focused ultrasound (FUS) (540 kHz) and anesthetic-loaded ultrasound-responsive nanodroplets to deliver pentobarbital to the PAG in normotensive (N = 27) and hypertensive (N = 20) male and female rats. BP, heart rate and plasma hormone content were collected before and after FUS exposure, and neuronal activity was mapped in the PAG using C-Fos and neuron subtype staining. Cavitation activity was monitored by detecting acoustic emissions from vaporizing nanodroplets, and neuromodulation was verified with immunohistochemistry.

Results: Systolic and diastolic BP were reduced for 6 h following a single sonication of the PAG (-37/-28 mmHg systolic/diastolic), and the offline effect was extended to 4 days with consecutive sonications combined with systemically injected pentobarbital-loaded nanodroplets. In contrast, FUS applied to the frontal cortex had no effect on BP. Immunohistochemistry revealed stimulation of inhibitory neurons in the PAG region, indicating that the hypotensive effect was associated with a GABAergic pathway. The acoustic emissions from vaporizing droplets were found to correlate with neuron activity and change in BP, offering the potential for real-time treatment monitoring using ultrasound.

Conclusions: This work has implications for developing a new treatment for hypertension that has greater safety and broader applicability for vulnerable patient populations.

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来源期刊

Brain Stimulation 医学-临床神经学

CiteScore

13.10

自引率

9.10%

发文量

256

审稿时长

72 days

期刊介绍： Brain Stimulation publishes on the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. Brain Stimulation aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) Original articles; b) Short Communications; c) Invited and original reviews; d) Technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) Letters to the Editor. Special issues of the journal will be considered based on scientific merit.