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Exploring Mechanisms Underlying SCF+G-CSF-Enhanced Recovery in ChronicTBI

Award Number: R01NS118166
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: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Exploring Mechanisms Underlying SCF+G-CSF-Enhanced Recovery in ChronicTBI - SUMMARY/ABSTRACT Traumatic brain injury (TBI) represents a public health crisis in the United States. TBI is a very common injury in young adults and causes long-term disabilities in cognition, learning and memory, emotional control, and sensory and motor function. A severe TBI can lead to lifelong physical and psychological problems and increase the risk of developing neurodegenerative diseases. Severe TBI in young adults is a significant public health problem and national burden because their lifelong disabilities, permanent productivity loss, and long- term daily care dependence not only seriously affect the life of an individual and their family but also create a heavy financial burden in the United States. In the traditional view, TBI is an event that only needs acute management and a brief period of rehabilitation. Today’s notion is that TBI is the onset of a chronic health condition that requires therapies for improving recovery months and years after TBI. However, no such a treatment is available in the chronic phase. The chronic phase exists in a long period from 3 or 6 months after TBI and throughout an individual’s life span. The lack of treatment to improve severe TBI recovery in the chronic phase is a critical problem for the country. Using a severe TBI model in young adult mice, we have demonstrated significant improvements in functional recovery by a combination treatment of stem cell factor (SCF) and granulocyte colony-stimulating factor (G- CSF) (SCF+G-CSF) in the chronic phase. However, it remains unclear how SCF+G-CSF treatment in the chronic phase of severe TBI improves functional recovery. The objective of this application is to determine the underlying mechanisms of the SCF+G-CSF-enhanced recovery in chronic TBI. Based on preliminary studies, we hypothesize that SCF+G-CSF-improved severe TBI recovery in the chronic phase is mediated by the enhancement of cerebral remyelination and neurostructural regeneration. Using the approaches of molecular and cellular biology, pharmacology, Cre-LoxP technology, 2-photon live brain imaging and neurobehavioral evaluation, this hypothesis will be tested through two Specific Aims. Aim 1 will determine how SCF+G-CSF treatment in the chronic phase of severe TBI enhances remyelination in cerebral white matter, and Aim 2 will define how SCF+G-CSF treatment in the chronic phase of severe TBI enhances neural structure regeneration. Searching for treatments to improve severe TBI recovery in the chronic phase is a highly-important-but-not- investigated field and an urgent national demand to improve the health of young adults living with severe TBI. It is expected that the accomplishment of the proposed mechanistic studies will significantly move the TBI research field forward by identifying a unique pharmacological approach to repair a severe TBI-damaged brain in the chronic phase.


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: 2026 ( Subtotal = $0 )
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/8/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $410,555 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/20/2025	NON-COMPETING CONTINUATION	$369,499
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	7/21/2025	NON-COMPETING CONTINUATION	$41,056
														Subtotal = $410,555

Issue Date FY: 2024 ( Subtotal = $398,239 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/8/2024	NON-COMPETING CONTINUATION	$28,740
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/21/2024	NON-COMPETING CONTINUATION	$369,499
														Subtotal = $398,239

Issue Date FY: 2023 ( Subtotal = $469,235 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/6/2023	SUPPLEMENT FOR EXPANSION	$19,560
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/29/2023	NON-COMPETING CONTINUATION	$410,555
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	3/30/2023	SUPPLEMENT FOR EXPANSION	$39,120
														Subtotal = $469,235

Issue Date FY: 2022 ( Subtotal = $410,555 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/7/2022	NON-COMPETING CONTINUATION	$410,555
														Subtotal = $410,555

Issue Date FY: 2021 ( Subtotal = $405,177 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/22/2021	NEW	$405,177
														Subtotal = $405,177

Grand Total All Awards = $2,093,761

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Exploring Mechanisms Underlying SCF+G-CSF-Enhanced Recovery in ChronicTBI

Award Number: R01NS118166

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: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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