Neural Engineering PhD Defense
George Hoeferlin
Advisor: Dr. Jeffrey R. Capadona
Intracortical microelectrodes (IMEs) are a type of brain-computer interface that allows for the recording of neural signals to communicate between the brain and computers. IMEs can be used to restore motor function in people with spinal cord injury, treatment of neurological disorders, and are a strong basic science tool for understanding the brain. Unfortunately, implanted IMEs consistently see a steady decline in recording ability over time, leading to failure of the device. Damage to the blood-brain barrier (BBB) from IME implantation is a key contributor to device failure. After BBB breach, neurotoxic molecules invade the brain and cause a downstream cascade of neuroinflammation and oxidative stress that further damages the BBB, brain tissue, and the IME itself. Attempts to minimize BBB damage to improve neuroinflammation and IME longevity have shown limited success. Given the lack of solutions to the chronic stability of neural recordings, further investigation into understanding and minimizing the effects of BBB damage is warranted.
In my dissertation, I investigate multiple strategies to mitigate and expand our understanding of how BBB damage can impact IME performance. Thermal damage to underlying vasculature because of cranial drilling has been shown to impact BBB permeability. To combat this, I developed a standardized surgical approach to limit surgeon variability and reduce thermal damage on the BBB. Next, I utilized the antioxidant dimethyl fumarate to promote BBB healing and reduce oxidative stress, resulting in acute improvements to IME function without long-term stability. Lastly, I investigated what unknown molecules enter the brain through the permeable BBB and contribute to neuroinflammation. I was the first to discover that gut-derived bacteria invade the site of implantation through the damaged BBB, which can be modulated with antibiotics to alter neuroinflammation and IME performance. New therapeutics can be developed utilizing this connection and merits further studies into how bacteria may influence other types of brain implants. Altogether, the outcomes of my dissertation address several areas of involvement between the BBB and IME function through surgical outcomes to mitigate BBB damage, antioxidant therapeutics to heal the BBB, and discovering a new approach for therapeutics to target invading bacteria after implantation.
Access to online presentation requires permission from gfh16@case.edu