Grant: Discovery Horizons

Injuries to the central nervous system (CNS) often result in permanent loss of sensory or motor functions which can severely impact an individual's wellness and quality of life. An emerging treatment uses functional electrical stimulation (FES) devices to bypass injured parts of the CNS and help to restore lost functions. For example, cochlear implants are already in wide use to help with hearing loss, while new technologies like intraspinal microstimulation (ISMS) are being developed to restore standing and walking functions in individuals with spinal cord injuries. These devices are implanted into the CNS which allows direct access to the intact neural circuits required to improve function, but also causes the body to react to the presence of a foreign device in the CNS. Microglia and astrocytes, two essential types of cells in the CNS, respond to these implants in order to protect the CNS from injury, but this response can slowly degrade the function of the devices. Despite many recent advances in device development, there remain many gaps in our understanding of how microglia and astrocytes interact with electrical stimulation. Since the CNS is an electrically active tissue and these cells are inherently able to interact and react to these electrical properties, we are seeking to expand our understanding of how cells sense and respond to electric fields to allow both an improved understanding of the function of microglia and astrocytes in the healthy CNS and inform improved design of electrodes for long-term use of FES devices. Our project intends to address three critical questions: 1 - How do microglia and astrocytes respond to electrical fields? These cells can detect patterns of activity from neurons as well as FES devices, but little is known about cellular mechanisms of this response. 2 - How can the device interface be engineered to improve biocompatibility? We will determine the cellular response to different stimulation patterns to help maximize biocompatibility. 3 - How does the cellular response to electrical fields vary between sexes? Cellular responses differ between the sexes and knowledge of these differences is critical to safe and effective device development. This research aims to bridge these knowledge gaps. Understanding how electrical fields affect microglia and astrocytes and optimizing device interfaces can lead to long-lasting, effective FES devices, improving the lives of individuals with neural injuries.