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Spinal serotonin in cerebral palsy

Award Number: R01NS091278
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: 09/30/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2021

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Spinal serotonin in cerebral palsy - DESCRIPTION (provided by applicant): The incidence of cerebral palsy is 1-2 per 1000 live births and has not declined in recent decades despite the improvement of neonatal care. Currently there is no cure for cerebral palsy and pathophysiology of motor deficits in this disorder is poorly understood. The proposal explores previously not described mechanism of muscle hypertonia in cerebral palsy after fetal hypoxia-ischemia brain injury acting via abnormally increased input of brain serotonin to spinal cord. We hypothesize that the elevated spinal serotonin increases spinal cord excitability and acts in development of motor deficits in cerebral palsy. A novel clinically relevant rabbit model of fetal hypoxia-ischemia, resulted in pronounced motor deficits in newborns, including muscle hypertonia, will be used to elucidate the proposed pathophysiological mechanism and therapeutic interventions. The proposed hypothesis will be tested using a combination of non-invasive imaging, electrophysiological recordings, biomechanical analysis of motor deficits and gene expression analysis. First, we will test whether white matter injury to the descending supraspinal projections and increased spinal serotonin explain postnatal muscle hypertonia after antenatal H-I independently or act synergistically. Second, we will test whether hypertonia could be directly caused by 5HT increasing intrinsic excitability of spinal motoneurons or due to altered synaptic excitation, including both pre- and postsynaptic modulation of synaptic inputs to motoneurons by 5HT, and decreased supraspinal inhibition due to white matter injury.


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: 2023 ( Subtotal = -$528 )
2023	2019	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/21/2022	NON-COMPETING CONTINUATION	-$528
														Subtotal = -$528

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/28/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $340,374 )
2019	2019	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/5/2019	NON-COMPETING CONTINUATION	$340,374
														Subtotal = $340,374

Issue Date FY: 2018 ( Subtotal = $340,375 )
2018	2018	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/12/2018	NON-COMPETING CONTINUATION	$340,375
														Subtotal = $340,375

Issue Date FY: 2017 ( Subtotal = $340,377 )
2017	2017	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/19/2017	NON-COMPETING CONTINUATION	$340,377
														Subtotal = $340,377

Issue Date FY: 2016 ( Subtotal = $340,379 )
2016	2016	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL STREET	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/7/2016	NON-COMPETING CONTINUATION	$340,379
														Subtotal = $340,379

Issue Date FY: 2015 ( Subtotal = $348,857 )
2015	2015	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL STREET	EVANSTON	IL	60201	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/24/2015	NEW	$348,857
														Subtotal = $348,857

Grand Total All Awards = $1,709,834

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Spinal serotonin in cerebral palsy

Award Number: R01NS091278

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: 09/30/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2021

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