# Neuronal Contribution to the Propagation of Inflammation in the Central Nervous System

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $144,793

## Abstract

Project Summary
 An intriguing phenomenon is observed in many neuroinflammation-based conditions, where neuroinflammatory
responses and neurophysiological changes occur distant to a focal brain lesion. This contributes to the therapeutic
challenges in managing neuroinflammatory diseases. Due to large diffusion distances, soluble factor-based signaling
is unlikely to cause distal neuroinflammatory responses, while focal neuroinflammation is too specific to be explained
by vascular transport of soluble factors. Our central hypothesis is that intra-axonal signaling and electrophysiological
signals (e.g., excitotoxicity) contribute to the transmission of neuroinflammatory triggers from the site of insult to
distal regions. Distinguishing the relative contributions of these complex factors in vivo, where many confounding
signals exist, is extremely difficult if not impossible. However, conventional in vitro tissue culture models are also
inadequate for addressing this problem because they do not recapitulate the spatial relationship of this phenomenon.
 In order to address this need, we will employ a microfluidic in vitro model that consist of two physically distinct
culture chambers (e.g., source and target, corresponding to immediate and distal anatomical regions) interconnected
by microchannels. This platform will allow for organotypic brain slice culture and the two chambers will be electrically
connected by axonal projections routed through the microchannels, while the chambers will remain chemically
separated by the high fluidic resistance of the channels and differential hydrostatic pressure at each chamber. Each
transparent chamber and the microchannels will allow for monitoring histological and biochemical changes and each
will contain multifunctional multiple electrode arrays for monitoring electrophysiological activity, allowing us to assess
the relative contribution of intra-axonal signaling and electrophysiological signal to the propagation of
neuroinflammation between discrete brain regions. Collectively, the pilot study is expected to (i) validate the
propagation of neuroinflammation observed in vivo and (ii) establish the foundation for future mechanistic studies of
neuroinflammation and its intra-axonal transmission with unprecedented control and detail.

## Key facts

- **NIH application ID:** 10042405
- **Project number:** 1R03NS118156-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Erkin Seker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $144,793
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10042405

## Citation

> US National Institutes of Health, RePORTER application 10042405, Neuronal Contribution to the Propagation of Inflammation in the Central Nervous System (1R03NS118156-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10042405. Licensed CC0.

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