Tiny devices called microelectrodes can be implanted in the brain to help restore movement, communication or other functions to people by listening to or sending signals to nerve cells.
These are often used to help people living with brain injuries or neurological conditions that affect movement, like Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis. They can also be implanted in people living with paralysis caused by spinal cord injuries. For these individuals, microelectrodes typically connect to a brain-computer interface (BCI), a device that can help a person communicate and function by helping them to use a computer or control other external devices.
But there is a problem with these microelectrodes: The brain sees them as something that does not belong there. This triggers inflammation around the implant, which can gradually reduce the effectiveness of the devices until they are no longer work effectively for the patient.
That is why University of Miami researchers Abhishek Prasad, an associate professor of biomedical engineering in the College of Engineering, and Juan Pablo de Rivero Vaccari, an associate professor of neurosurgery at the Miller School of Medicine, along with Jean-Hubert de Olivier, an associate professor of chemistry at the University of New Mexico, are starting a new five-year research study supported by the National Institutes of Health to explore how to reduce the body's instinct to trigger inflammation around these electrodes so they can work better for the people relying on them.
"We want to understand more about the biology and immune response happening around these electrodes, so we can help them to last longer and to be more effective," Prasad said.
It is a topic that both Prasad and de Rivero Vaccari have touched on before in their research at The Miami Project to Cure Paralysis, but this work is becoming even more relevant as more companies are developing BCIs for people living with paralysis.
A quick but lasting reaction
As soon as a microelectrode device is implanted in the brain—typically in the motor cortex —the body launches its natural defense system, similar to what happens when a person gets a splinter. This causes inflammation around the device as the brain tries to protect itself from the foreign object, said de Rivero Vaccari.
While this immune response is meant to help the body heal, unfortunately, over time, the inflammation damages nearby brain cells and forms scar tissue around the microelectrode, making it harder for the device to function properly.
One part of this defense system involves structures called inflammasomes, or multiprotein complexes that act like alarm sensors. When they detect damage or an unwanted object, they trigger inflammation.
"The chemical mechanisms that happen as a result of these processes make for a perfect storm that contributes to these microelectrodes losing their function, or causing them to malfunction," de Rivero Vaccari said.
Researchers know that inflammasomes play an important role in the body's response to brain injuries, but they still do not fully understand how they affect implanted devices and whether controlling the inflammasomes could help those devices work better, Prasad said.
"We know that these electrodes eventually stop working and a large part of that is from the immune response, so we are focusing on that to see if we can improve the function of these devices," Prasad said.
Testing a possible intervention
As technology advances, more people each year who are living with brain or spinal cord injuries or neurological diseases are opting to have a small electrode implanted in their brain to help them regain some form of movement or better control of their body. Prasad points out that more than 200,000 deep brain stimulation devices with electrodes have been implanted in people's brains worldwide to treat neurological and neuropsychiatric disorders. And many people with spinal cord injuries are also opting to join clinical trials for new brain-computer interfaces, but estimates are around 100 individuals so far because most of these are still experimental.
To ease the body's reaction of these devices, de Rivero Vaccari's lab is working on developing therapeutics to block the aggressive immune responses, and they will be testing one drug as part of the new study. The therapeutic is called IC 100, and it is an injectable monoclonal neutralizing antibody that has been able to prevent some of the inflammation associated with implanted microelectrodes in previous animal trials.
"We already have some preliminary data showing that this works," de Rivero Vaccari said. "Through this work, we hope that we can decrease the inflammatory response to preserve tissue integrity and the long-term function of these microelectrodes. That will translate into better quality of life for these patients, who right now have access to a life-changing technology, but one that has an expiration date. If we can help to prolong their quality of life, that would be an important gain."
Beyond that, the research could help these scientists understand how inflammation progresses in general, Prasad said, which happens with many other conditions. It also could give medical professionals a pathway to prevent inflammation from foreign objects implanted in the body, as occurs in many orthopedic surgeries and some cardiovascular surgeries, Vaccari added.
