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Investigating the source and the action behind shunt obstruction in the treatment of pediatric hydrocephalus

Award Number: R01NS094570
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Investigating the source and the action behind shunt obstruction in the treatment of pediatric hydrocephalus - PROJECT SUMMARY Hydrocephalus, an imbalance between cerebrospinal fluid production and absorption, is diagnosed in more than 1 in 500 people in the United States. Approximately 80% of these patients will suffer long-term neurological deficits. Genetic diseases, meningitis, subarachnoid hemorrhage, stroke, traumatic brain injury, or tumors cause hydrocephalus. The common treatment for all hydrocephalus patients is CSF drainage by shunting. Despite all our efforts, shunts still have the highest failure rate of any neurological device. A shocking 85% of shunts fail after just ten years. Failed shunts are plagued with astrocytes and macrophages, but we still do not understand the process by which these cells are pulled in, migrate, and grow. In our first aim, we identify what patient conditions contribute to tissue contact and what variables trigger tissue pull in into shunt catheter holes. We clearly define physical variables that create instances of tissue pull in using computational fluid dynamics and a benchtop model (“Brain on a Bench”). We continue the use of this system in Aims 2 and 3. In this way, we investigate what single or repetitive events cause shunt catheter contact and tissue pull in with the ventricular wall, parenchyma, or choroid plexus. In our second aim, we determine if cell growth is a necessary component to shunt obstruction after contact with a tissue source occurs. We examine the growth, proliferation, and activation state of the cells following single or repetitive contact with ventricular wall, parenchyma, and choroid plexus just as we did in Aim 1. In our final aim, we use our heightened awareness of tissue pull in and tissue growth to understand how changes to shunt design can influence shunt obstruction. We prioritize the clinical conditions shown to exacerbate tissue contact and test under physical variables that show direct pull in and growth of ventricular wall, parenchyma, and choroid plexus. In summary: our patient data informs us of the patient conditions that correlate to contact of ventricular wall, parenchyma, and choroid plexus. Benchtop and computational fluid dynamics models prioritize these environmental conditions while systematically testing what variables cause tissue pull in and growth. Strategies to prevent obstruction by inhibition of pull in and growth are tailored for ideal performance under the conditions set by our patient and benchtop data. Altogether, these data improve our mechanistic understanding of shunt obstruction necessary to and narrow our area of focus for improved treatment of hydrocephalus.


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: 2025 ( Subtotal = $525,636 )
2025	2025	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	8	5/22/2025	NON-COMPETING CONTINUATION	$525,636
2025	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	5/22/2025	NON-COMPETING CONTINUATION	$0
2025	2023	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	1/22/2025	COMPETING CONTINUATION	$17,917
2025	2020	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/22/2025	NON-COMPETING CONTINUATION	-$17,917
														Subtotal = $525,636

Issue Date FY: 2024 ( Subtotal = $511,734 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	8/28/2024	NON-COMPETING CONTINUATION	$511,734
														Subtotal = $511,734

Issue Date FY: 2023 ( Subtotal = $575,066 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	5/30/2023	COMPETING CONTINUATION	$575,066
														Subtotal = $575,066

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/18/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $474,352 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/18/2020	NON-COMPETING CONTINUATION	$474,352
														Subtotal = $474,352

Issue Date FY: 2019 ( Subtotal = $403,745 )
2019	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/24/2019	NON-COMPETING CONTINUATION	$403,745
														Subtotal = $403,745

Issue Date FY: 2018 ( Subtotal = $403,776 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/18/2018	NON-COMPETING CONTINUATION	$375,853
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/20/2018	SUPPLEMENT FOR EXPANSION	$27,923
														Subtotal = $403,776

Issue Date FY: 2017 ( Subtotal = $376,136 )
2017	2017	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/1/2017	NON-COMPETING CONTINUATION	$376,136
														Subtotal = $376,136

Issue Date FY: 2016 ( Subtotal = $393,272 )
2016	2016	WAYNE STATE UNIVERSITY	5700 CASS SUITE 4602	DETROIT	MI	48202	WAYNE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/8/2016	NEW	$393,272
														Subtotal = $393,272

Grand Total All Awards = $3,663,717

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Investigating the source and the action behind shunt obstruction in the treatment of pediatric hydrocephalus

Award Number: R01NS094570

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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