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Strategy to Potentiate Rehabilitation after TBI

Award Number: R01NS116383
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: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Strategy to Potentiate Rehabilitation after TBI - Abstract Metabolic depression (MD) occurs during the acute period of TBI and this impairs the ability of neuronal circuits to meet local activity demand, which in turn could limit the success of rehabilitative strategies, and functional outcome. Although most neurons survive mild or moderate TBI, at least acutely, they cannot operate efficiently and this severely compromises brain function, which may lead to persistent behavioral deficits. This manifests as a loss of correlated functional activity using resting state functional magnetic resonance imaging (rsFMRI) and is typically reported using a connectomic analysis of brain network function. There remains much to learn about how to treat the injured brain, how the functional trajectory of neurons evolves with time, and the dependence on the extent and major pathologic subtype of the initial injury. We propose combined rsFMRI, behavior and molecular studies of metabolism and synaptic plasticity that will provide a longitudinal analysis of injury to investigate how MD manifests in altered functional connectivity and brain reorganization chronically. We will use the information gained to provide insight on how the small molecule agonist of TrkB receptors - 7,8- dihydroxyflavone (DHF) will alter the functional trajectory of the injured brain through reduction of MD acutely, followed by enhancement of synaptic plasticity and cognitive outcome chronically. By modelling clinical situations of early post-injury rehabilitation versus rehabilitation that is delayed due to additional injuries, we will determine whether an intervention with DHF will mitigate the effects of acute MD, followed by, or simultaneously with the reinstitution of function using a period of early or delayed exercise. We propose studies that will test whether either intervention, alone or in combination, can be delayed but still provide a significant boost to brain connectivity and functional outcome. We will conduct these studies in both male and female rats, and will use new statistically-driven methods that provide a level of confidence to enable subject-level analysis for discrimination of burden of tissue damage, regardless of the actual injury severity. We will employ these covariates of MD, tissue swelling and atrophy, as well as exercise level, to derive a statistically robust analysis of whether off-setting MD acutely, will potentiate the effects of rehabilitation.


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 = $542,762 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/11/2024	NON-COMPETING CONTINUATION	$542,762
														Subtotal = $542,762

Issue Date FY: 2024 ( Subtotal = $584,976 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/21/2023	NON-COMPETING CONTINUATION	$542,762
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/23/2024	NON-COMPETING CONTINUATION	$42,214
														Subtotal = $584,976

Issue Date FY: 2023 ( Subtotal = $603,068 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/31/2023	NON-COMPETING CONTINUATION	$60,306
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/7/2022	NON-COMPETING CONTINUATION	$542,762
														Subtotal = $603,068

Issue Date FY: 2022 ( Subtotal = $603,068 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/28/2022	NON-COMPETING CONTINUATION	$60,305
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/1/2021	NON-COMPETING CONTINUATION	$542,763
														Subtotal = $603,068

Issue Date FY: 2021 ( Subtotal = $628,353 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/27/2020	NEW	$628,353
														Subtotal = $628,353

Grand Total All Awards = $2,962,227

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Strategy to Potentiate Rehabilitation after TBI

Award Number: R01NS116383

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: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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