# Novel tools for in vitro electrophysiology and neurotrauma modeling

> **NIH NIH R01** · ENDEAVOR HEALTH CLINICAL OPERATIONS · 2020 · $169,615

## Abstract

Traumatic brain injury (TBI) remains a significant cause of death and disability in its own right in the United
States and is an important risk factor for other neurodegenerative conditions. However, there are currently
no approved therapies for TBI and its long term consequences are difficult to predict. More than 30 major
phase III trials have failed without a single success so discovery of a universal therapy seems increasingly
unlikely. NINDS and other federal agencies have committed tens of millions of dollars to large,
observational, human studies of TBI. These studies are genotyping and deeply phenotyping TBI patients
with the goal of personalizing therapy. These efforts have already revealed fascinating correlations between
genotype and TBI outcome. However, genes cannot be switched on an off in humans for ethical reasons.
Therefore, new tools are necessary to move from detecting correlations to testing hypotheses. This
challenge has been addressed in other diseases using human, in vitro models. Human neurons generated
from patients using stem cell technology retain the genetic identity of the patient. Also, genetic variants can
be changed one at a time in these cells. Therefore, hypotheses about the role of genotype in disease can
be tested in human, in vitro models but only if the disease pathology can reproduced in vitro. Reproducing
neurotrauma pathology in vitro requires special tools because it depends intrinsically on a mechanical insult.
The goal of this proposal is to provide new tools for modeling neurotrauma in vitro that can take advantage
of exciting recent developments in human, in vitro cultures. Target-driven drug discovery is difficult in
neurotrauma because the molecular mechanisms are complex. Phenotypic drug discovery is therefore
preferable but it can succeed only if it addresses a clinically relevant phenotype. In vitro, electrical field
recordings are attractive because they are analogous to electroencephalography, which is commonly used
to assess TBI patients. This work will contribute the first, multi-electrode array (MEA) that can acquire field
recordings from a high throughput, in vitro model. Brain organoids reproduce aspects of disease that cannot
be reproduced in 2D cultures. However, electrical field recordings are difficult to acquire from brain
organoids because conventional, multi-electrode arrays are designed for adherent cultures while brain
organoids require ultra-low adherence conditions. Therefore, novel, sub-millimeter scale structures are
proposed that will enclose an organoid inside an array of electrodes without adhering to it so that long term
measures of electrical activity and connectivity can be made. These 3D MEAs will contribute new insights to
many neurological disorders beside neurotrauma. Currently, there are no tools available that can apply a
biofidelic, mechanical insult to an organoid culture. The proposed work will develop such a tool. In
combination, these new tools will open new h...

## Key facts

- **NIH application ID:** 9861811
- **Project number:** 1R01NS113935-01
- **Recipient organization:** ENDEAVOR HEALTH CLINICAL OPERATIONS
- **Principal Investigator:** John D Finan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,615
- **Award type:** 1
- **Project period:** 2020-02-15 → 2020-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861811

## Citation

> US National Institutes of Health, RePORTER application 9861811, Novel tools for in vitro electrophysiology and neurotrauma modeling (1R01NS113935-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861811. Licensed CC0.

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