Neurally implanted devices transmit targeted electrical stimulation to the nervous system, to modify abnormal brain activity. It is usually assumed that neurons are the only important brain cells that need to be stimulated by these devices. But new research suggests that it could also be important to target the supportive glial cells surrounding the neurons.

“Glial cells are the most abundant in the central nervous system and critical to the function of the neuronal network. The most obvious function of glial cells has been related to their role in forming scar tissue to prevent the spread of injury and neuronal degeneration, but so much about their role in the brain is unknown.

From providing growth factor support and ensuring proper oxygen and nutrient delivery to the brain to trimming of obsolete synapses and recycling waste products, recent findings show that glial cells do much more to ensure brain activity is optimized,"

said Takashi Kozai, assistant professor of bioengineering at the University of Pittsburgh’s Swanson School of Engineering.

Glial Cell Activity

The slow, muted signals of glial cells are much more challenging to detect than the dynamic electrical activity of neurons. New advancements in technology allows researchers like Kozai to detect the subtleties of glial cell activity, and these observations are shedding new light on current issues plaguing implant devices and the treatment of neurological disease.

“Dysfunction in glial cells has been implicated as a cause and/or major contributor to an increasing number of neurological and developmental diseases. Therefore, it stands to reason that targeting these glial cells (in lieu of or in combination with neurons) may dramatically improve current treatments,"

Kozai explaied.

He leads the Bionic Lab at Pitt, where researchers are investigating the biological tissue response to implantable technologies. Although there have been many advancements in neural implant technology in recent years, their underlying effects and reasons for their failure still puzzle scientists.

Advanced Microscopy

By using advanced microscopy techniques, researchers can create more detailed neurological maps and imaging.

“By combining in vivo multiphoton microscopy and in vivo electrophysiology, our lab is better able to visualize how cells move and change over time in the living brain and explain how changes in these glial cells alter the visually evoked neural network activity,” said Kozai. “Using this approach to better understand these cells can help guide implant design and success."

Kozai’s lab is currently working with Franca Cambi, professor of neurology at Pitt, on a project to understand the role of another type of glial cell on brain injury and neuronal activity.

[caption id=“attachment_94078” align=“aligncenter” width=“680”]glial cells diagram Steven L Wellman/BionicLab.ORG[/caption]

Oligodendrocyte Progenitor Cells, or OPCs, are progenitor cells — similar to stem cells — that have the capacity to differentiate during tissue repair.

“Although OPCs have been understudied in brain-computer interface, they form direct synapses with neurons and are critical to their repair,” said Kozai. “As progenitor cells, they have the capacity to differentiate into a variety of cells, including neurons. The technology is advancing to the point in which we can have a much better understanding of how the brain works comprehensively, rather than just focusing on neurons because their electrical signals make them appear brighter when imaging the brain."

Support for the study’s authors came from the National Institutes of Health and The Grainger Foundation.

Joseph W. Salatino, Kip A. Ludwig, Takashi D. Y. Kozai & Erin K. Purcell Glial responses to implanted electrodes in the brain Nature Biomedical Engineering 1, 862–877 (2017) doi:10.1038/s41551-017-0154-1

Top Image: depiction of the brain glial cell response towards site injury upon insertion of neural interface probe track (rectangular hole), which disrupts the maintenance of their important regulatory roles. Credit: TDY Kozai/BionicLab.ORG

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