Modulating the (sympathetic) nervous system with anesthetic-loaded nanodroplets

Neurotransmitters are used by the sympathetic nervous system to signal danger and regulate the body. Exploiting these neural and hormonal responses may hold promise for new treatments for hypertension, anxiety, and chronic stress. We have developed a platform using transcranial focused ultrasound, bubble activity from vaporizing nanodroplets, and locally released neuroactive substances to perturb the sympathetic nervous system. By sonicating the periaqueductal grey region (540 kHz, 10 ms pulse length, 1 Hz PRF, 0.275–1.65 MPa), with and without systemically injected nanodroplets, local brain activity is altered, neurotransmitters and hormones are detected in the bloodstream, and systolic and diastolic blood pressure is reduced. By mapping the suppression and activation of neurons, and identifying the specific neuron subtype, we compare midbrain and frontal cortex stimulation. We compare healthy and hypertensive rodents and assess differences in cavitation activity across sex, brain region, and disease state. We investigate the influence of inhaled isoflurane level, which was found to mask the hypotensive effect of FUS during sedation compared to the conscious state. Understanding how transcranial focused ultrasound and cavitation activity, in combination with locally delivered anesthetics, affects the sympathetic nervous system, could have a significant impact in treating hypertension, anxiety, and chronic stress.