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Interplay of Neuroinflammation and Tau Transport in a Microfluidic Primary Neural Cell Tri-Culture Model

Award Number: R03NS118156
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$605 )
2024	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/6/2024	SUPPLEMENT FOR EXPANSION	-$605
														Subtotal = -$605

Issue Date FY: 2021 ( Subtotal = $71,361 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/23/2021	SUPPLEMENT FOR EXPANSION	$71,361
														Subtotal = $71,361

Issue Date FY: 2020 ( Subtotal = $144,793 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/15/2020	NEW	$144,793
														Subtotal = $144,793

Grand Total All Awards = $215,549

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Interplay of Neuroinflammation and Tau Transport in a Microfluidic Primary Neural Cell Tri-Culture Model

Award Number: R03NS118156

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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