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The Impact of Diffuse Mild Brain Injury on Clinical Outcomes in Children

Award Number: R01NS098494
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: 07/01/2016
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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The Impact of Diffuse Mild Brain Injury on Clinical Outcomes in Children - Abstract. Pediatric mild traumatic brain injury (pmTBI) remains a large public health concern due to the number of youths affected each year and the risk for permanently altered neurodevelopmental trajectories. Emerging evidence from our ongoing R01 project and other independent studies suggests a potential mismatch between symptomatic (self-reported post-concussive symptom load; PCS) and physiological recovery as indexed by advanced imaging biomarkers. This exponentially increases the risk for a cumulative and potentially super- additive second injury if premature decisions are made about return to activity. The proposed renewal application builds upon a very successful R01 program (29 publications, over-recruitment [N=566 unique participants] during COVID-19 pandemic, high [>80%] retention rates) that demonstrated diffuse microstructural and vascular injuries that persisted up to 4 months post-injury. The proposed renewal further elucidates the mechanisms underlying these diffuse axonal and vascular injuries, including altered myelin volume fractions, neuroinflammation (quantified through myo-inositol and the anti-oxidant glutathione in cerebro), arterial transit times, as well as the balance between excitatory (glutamate and glutamine) and inhibitory (γ-Aminobutyric acid; GABA) neurotransmission that is critical for the maintenance of neuronal homeostasis. These imaging markers will be complimented by traditional (e.g., neurofilament light [NFL], glial fibrillary acid protein [GFAP]) and novel blood- based biomarkers of blood-brain barrier breach and endothelial damage. Our new preliminary data provides evidence that NFL remains elevated up to 4 months post-injury and is associated with white and grey matter abnormalities on advanced imaging, with initial feasibility studies established for all other novel imaging and blood-based biomarkers. To achieve our renewal objectives, 178 pmTBI (ages 13-18) and 132 matched (age, sex and social economic status) healthy controls (HC) will be enrolled across acute (1-48 hours post-injury; blood and minimal clinical assessments); sub-acute (SA: 3-10 days; full clinical, imaging and blood collection assessments) and early chronic (EC: ~4 months; full clinical, imaging and blood collection assessments) visits. Patients and HC, as well as their primary caregivers, are assessed with a comprehensive Common Data Elements clinical battery to characterize cognitive, physical and emotional sequelae of concussion. Our published data demonstrate that equivalent assessments of clinical and biomarker data in HC are necessary to disambiguate trauma effects from sex and age-related typical neurodevelopment, which occurs even within a 4- month assessment window and is unique to pediatric populations (i.e., cannot be inferred from adults).


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 = $821,974 )
2025	2025	LOVELACE BIOMEDICAL RESEARCH INSTITUTE	2425 RIDGECREST DR SE	ALBUQUERQUE	NM	87108	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	4/14/2025	COMPETING CONTINUATION	$821,974
														Subtotal = $821,974

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	MIND RESEARCH NETWORK	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,408,563 )
2021	2021	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/30/2021	NON-COMPETING CONTINUATION	$1,408,563
														Subtotal = $1,408,563

Issue Date FY: 2020 ( Subtotal = $1,484,846 )
2020	2020	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/20/2020	NON-COMPETING CONTINUATION	$1,484,846
														Subtotal = $1,484,846

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/15/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $1,558,099 )
2018	2018	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	6/4/2018	SUPPLEMENT FOR EXPANSION	$890,249
2018	2018	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/26/2018	NON-COMPETING CONTINUATION	$66,784
2018	2018	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/12/2018	NON-COMPETING CONTINUATION	$601,066
														Subtotal = $1,558,099

Issue Date FY: 2017 ( Subtotal = $664,495 )
2017	2017	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/19/2017	NON-COMPETING CONTINUATION	$598,046
2017	2017	MIND RESEARCH NETWORK, THE	1101 YALE BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/7/2017	NON-COMPETING CONTINUATION	$66,449
														Subtotal = $664,495

Issue Date FY: 2016 ( Subtotal = $698,677 )
2016	2016	THE MIND RESEARCH NETWORK	1101 YALE BOULEVARD NORTHEAST	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/16/2016	NEW	$698,677
														Subtotal = $698,677

Grand Total All Awards = $6,636,654

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The Impact of Diffuse Mild Brain Injury on Clinical Outcomes in Children

Award Number: R01NS098494

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: 07/01/2016

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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