Jorge Pincay ’20

Over the years research in neuroscience has led to the development of brain implants, called microelectrodes that can help restore essential motor and sensory functions. This technology has become beneficial for those that suffer from head injury and neurodegenerative disease. The limitations of this technology lie within the immunological response that comes about shortly after implantation. This immune response, which is governed by the microglia cells of the CNS, can cause inflammation and neurodegeneration. Microglia cells mediate neurodegeneration by stimulating increased production of reactive oxygen and nitrogen species (RONS)in the neural tissue. Normally this oxidative stress is kept under control by an enzyme known as superoxide dismutase (SOD). Recently, researchers in Pittsburg were able to develop a compound that mimics the function of SOD and acts as a coating for implantable microelectrodes. This compound is referred to as the immobilizable superoxide dismutase mimic (iSODm), and it is a derivative of a previously made compound known as the superoxide dismutase mimic (SODm).

This compound, iSODm, along with other various antioxidant compounds (SODm, MnTBAP, and  resveratrol) were tested for their ability to scavenge for RONS by the cytochrome C assay. A good antioxidant compound will be able to scavenge for the oxidative species effectively and prevent the reduction of cytochrome C. Of all the antioxidant compounds tested only iSODm and SODm were able to prevent the reduction of cytochrome C.

Microglia cells from the HAPI cell line were used as an in vitro model to further test the antioxidative effects of iSODm. Microglia cells were plated on glass that either contained one of the various antioxidants or no antioxidant at all. These microglia cells were then incubated with different compounds to stimulate the immune response and therefore increase the production of RONS. All cells experienced a 110% increase in cytochrome C reduction. Only the cells plated on glass containing iSODm or SODm were able to return to pre-stimulation levels of cytochrome C reduction. 

The antioxidative effects of iSODm were then tested on the brains of rats. Probes coated with and without iSODm were implanted into the lateral cortices of rat brains to assess the effects of iSODm on the neural tissue. A caspase-3 marker was used to measure the amount of apoptosis occurring in neural tissue after implantation. Results showed that iSODm coated probes were able to  significantly reduce the amount of apoptosis occurring in neurons within 0μm-25μm. In addition to the caspase-3 marker, 4-hydroxynonenal (4HNE), a compound produced during increased oxidative stress, was measured to further assess iSODm. Once again the levels of 4HNE were significantly reduced within 0μm-25μm, further indicating that iSODm was mitigating the production of RONS effectively.

More research must be done on this compound, specifically, on the compatibility of the compound with human tissue in order for it to advance from the lab and into human treatment. However, with the potential that this compound has, it could one day be possible to receive neural implants without experiencing any adverse effects at all.

Reference:

1. X. S. Zheng, N. R. Snyder, K. Woeppel et al., A superoxide scavenging coating for improving tissue response to neural implants, Acta Biomaterialia, doi.org/10.1016/j.actbio.2019.08.032
2. Image retrieved from: https://www.nbcnews.com/mach/science/brain-implant-boosts-memory-first-time-ever-ncna821016