Presented By: Biomedical Engineering
Ph.D. Defense: Ahmad Asif A Jiman
Modulating and Monitoring Autonomic Nerves for Glycemic Control
NOTICE: This event will be hosted via Zoom. You can log in with this link:
https://umich.zoom.us/j/329580834
Meeting ID: 329-580-834
Diabetic patients suffer from a long-term condition that results in high blood glucose levels (hyperglycemia). Many medications for diabetes lose their glycemic control effectiveness over time and patient compliance to these medications is a major challenge. Glycemic control is a vital continuous process and is innately regulated by the endocrine and autonomic nervous systems. There is an opportunity for developing an implantable and automated treatment for diabetic patients by accurately detecting and altering neural activity in autonomic nerves. The renal and vagus nerves contribute in glycemic control and are potential targets for this proposed treatment. This dissertation investigated stimulation of renal nerves for glycemic control, assembled an implantation procedure for neural interface arrays designed for autonomic nerves, and demonstrated high-fidelity physiological signals in the vagus nerve of rats.
Stimulation of renal nerves at kilohertz frequency (33 kHz) showed a notable average increase in urine glucose excretion (+24.5%). In contrast, low frequency (5 Hz) stimulation of renal nerves showed a decrease in glucose excretion (−40.4%). However, these responses may be associated with urine flow rate.
Kilohertz frequency stimulation (50 kHz) of renal nerves in diabetic rats showed a significant average decrease (-168.4%) in blood glucose concentration rate, and an increase (+18.9%) in the overall average area under the curve for urine glucose concentration, with respect to values before stimulation.
An innovative procedure was assembled for the chronic implantation of novel intraneural MIcroneedle Nerve Arrays (MINAs) in rat vagus nerves. Two array attachment approaches (fibrin sealant and rose-bengal bonding) were investigated to secure non-wired MINAs in rat vagus nerves. The fibrin sealant approach was unsuccessful in securing the MINA-nerve interface for 4- and 8-week implant durations. The rose-bengal coated MINAs were in close proximity to axons (≤ 50 μm) in 75% of 1-week and 14% of 6-week implants with no significant harm to the implanted nerves or the overall health of the rats.
Using Carbon Fiber Microelectrode Arrays (CFMAs), physiological neural activity was recorded on 51% of inserted functional carbon fibers in rat vagus nerves, and 1-2 neural clusters were sorted on each carbon fiber with activity. The mean peak-to-peak amplitudes of the sorted clusters were 15.1-91.7 µV with SNR of 2.0-7.0. Propagation of vagal signals were detected in the afferent direction at conduction velocities of 0.7-1.0 m/sec, and efferent signals at 0.7-8.8 m/sec, which are within the conduction velocity range of myelinated and unmyelinated vagus fibers. Furthermore, changes in vagal nerve activity were monitored in breathing and blood glucose modulated conditions.
Overall, this dissertation investigated modulation of neural activity for glycemic control, assembled a new chronic implantation procedure for nerve interface arrays, and monitored physiological signaling in an autonomic nerve. Future work is needed to fully understand the physiological neural signaling, and evaluate the long-term tissue reactivity and recording integrity of implanted electrodes in autonomic nerves. This work supports the potential development of an alternative implantable treatment modality for diabetic patients by modulating and monitoring neural activity in autonomic nerves.
Date: Tuesday, March 24, 2020
Time: 10:00 AM
Location: North Campus Research Complex (NCRC), B10-G64
Chair: Dr. Tim M. Bruns
https://umich.zoom.us/j/329580834
Meeting ID: 329-580-834
Diabetic patients suffer from a long-term condition that results in high blood glucose levels (hyperglycemia). Many medications for diabetes lose their glycemic control effectiveness over time and patient compliance to these medications is a major challenge. Glycemic control is a vital continuous process and is innately regulated by the endocrine and autonomic nervous systems. There is an opportunity for developing an implantable and automated treatment for diabetic patients by accurately detecting and altering neural activity in autonomic nerves. The renal and vagus nerves contribute in glycemic control and are potential targets for this proposed treatment. This dissertation investigated stimulation of renal nerves for glycemic control, assembled an implantation procedure for neural interface arrays designed for autonomic nerves, and demonstrated high-fidelity physiological signals in the vagus nerve of rats.
Stimulation of renal nerves at kilohertz frequency (33 kHz) showed a notable average increase in urine glucose excretion (+24.5%). In contrast, low frequency (5 Hz) stimulation of renal nerves showed a decrease in glucose excretion (−40.4%). However, these responses may be associated with urine flow rate.
Kilohertz frequency stimulation (50 kHz) of renal nerves in diabetic rats showed a significant average decrease (-168.4%) in blood glucose concentration rate, and an increase (+18.9%) in the overall average area under the curve for urine glucose concentration, with respect to values before stimulation.
An innovative procedure was assembled for the chronic implantation of novel intraneural MIcroneedle Nerve Arrays (MINAs) in rat vagus nerves. Two array attachment approaches (fibrin sealant and rose-bengal bonding) were investigated to secure non-wired MINAs in rat vagus nerves. The fibrin sealant approach was unsuccessful in securing the MINA-nerve interface for 4- and 8-week implant durations. The rose-bengal coated MINAs were in close proximity to axons (≤ 50 μm) in 75% of 1-week and 14% of 6-week implants with no significant harm to the implanted nerves or the overall health of the rats.
Using Carbon Fiber Microelectrode Arrays (CFMAs), physiological neural activity was recorded on 51% of inserted functional carbon fibers in rat vagus nerves, and 1-2 neural clusters were sorted on each carbon fiber with activity. The mean peak-to-peak amplitudes of the sorted clusters were 15.1-91.7 µV with SNR of 2.0-7.0. Propagation of vagal signals were detected in the afferent direction at conduction velocities of 0.7-1.0 m/sec, and efferent signals at 0.7-8.8 m/sec, which are within the conduction velocity range of myelinated and unmyelinated vagus fibers. Furthermore, changes in vagal nerve activity were monitored in breathing and blood glucose modulated conditions.
Overall, this dissertation investigated modulation of neural activity for glycemic control, assembled a new chronic implantation procedure for nerve interface arrays, and monitored physiological signaling in an autonomic nerve. Future work is needed to fully understand the physiological neural signaling, and evaluate the long-term tissue reactivity and recording integrity of implanted electrodes in autonomic nerves. This work supports the potential development of an alternative implantable treatment modality for diabetic patients by modulating and monitoring neural activity in autonomic nerves.
Date: Tuesday, March 24, 2020
Time: 10:00 AM
Location: North Campus Research Complex (NCRC), B10-G64
Chair: Dr. Tim M. Bruns
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