Remotely Programmable Deep Brain Stimulator Combined with an Invasive Blood Pressure Monitoring System for a Non-Tethered Rat Model in Hypertension Research

Abstract

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device's pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.

Keywords: caudal ventrolateral medulla; closed-loop stimulation; deep brain stimulation; hypertension; rat model; telemetry.

Figure 1

Parts of the measurement system.

Figure 2

Software architecture.

Figure 3

Ten seconds of calibrated data.

Figure 4

A Wistar rat equipped with the device is shown on the left. The device with an electrode, Wi-Fi module, blood pressure sensor, and catheter system is shown on the right.

Figure 5

Mean arterial pressure change during the stimulation period intraoperatively marked in purple.

Figure 6

Typical graphs show a change in mean arterial blood pressure during two weeks of the experiment: response to stimulation on the left side and lack of response on the right side. “Stimulation OFF” and Stimulation ON” periods are shown in different shades of grey.

Figure 7

Device calibration data showing blood pressure output in mV on different experimental days. dF and p values of ANOVA are presented in the chart.

Figure 8

Brain stimulation pulse recordings. Pulse settings: Apulse = 100 µA, Tpulse = 100 µs. (a) Oscilloscope recording on 1000-ohm resistor; (b) Internal microcontroller’s ADC recording on 1000-ohm resistor; (c) In vivo internal microcontroller ADC recording.