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Developmental disruption of brain tissue oxygen regulation and deficiency of learning after neonatal anesthesia exposure

Award Number: R01GM112715
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence. However, little is known about the methods which can be used to evaluate these impairments. Our preliminary and published data suggest that changes in regional resting state functional MRI (rsfMRI) can reflect the status of local neuronal networks and can have a predictive value for anesthesia-induced learning deficiency. Regional rsfMRI depends on the regulation of local brain tissue oxygen. Based on published and preliminary data we hypothesize that brain tissue oxygen and regional rsfMRI regulation are modulated by GABAergic neurons (interneurons) but neonatal anesthesia disrupts the development of this modulation and produces a specific signature on the rsfMRI signal. In Aim 1 we will determine the mechanisms responsible for regional rsfMRI and brain tissue oxygen regulation under normal conditions and after neonatal anesthesia exposure by using brain tissue oxygen, BOLD fMRI, electrophysiological recordings, local pharmacological and optogenetic approach in adults. In Aim 2 we will determine how the development of regional rsfMRI and brain tissue oxygen fluctuations is affected by neonatal anesthesia exposure and find time points when rsfMRI can predict the future behavioral deficiency. Behavioral tests, local rsfMRI, brain tissue oxygen, and neuronal activity will be recorded in across multiple time points after neonatal anesthesia exposure and in the control group. The results of the proposed work will provide a clear picture of how the regulation of brain tissue oxygen is affected by neonatal anesthesia exposure and will offer strong translational value of resting-state fMRI to predict learning deficiency.


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 = $436,017 )
2023	2023	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	001	8	8/8/2023	NON-COMPETING CONTINUATION	$346,150
2023	2023	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	7	5/24/2023	SUPPLEMENT FOR EXPANSION	$89,867
														Subtotal = $436,017

Issue Date FY: 2022 ( Subtotal = $346,150 )
2022	2022	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	7	8/19/2022	NON-COMPETING CONTINUATION	$346,150
2022	2021	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	002	6	8/23/2022	COMPETING CONTINUATION	$123,034
2022	2020	NORTHSHORE UNIVERSITY HEALTHSYSTEM	SUITE 301	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	001	5	8/23/2022	NON-COMPETING CONTINUATION	-$123,034
														Subtotal = $346,150

Issue Date FY: 2021 ( Subtotal = $291,698 )
2021	2021	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	002	6	9/29/2021	COMPETING CONTINUATION	$0
2021	2021	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	001	6	9/16/2021	COMPETING CONTINUATION	$291,698
2021	2020	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	5	9/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $291,698

Issue Date FY: 2020 ( Subtotal = $298,045 )
2020	2020	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	5	5/20/2020	NON-COMPETING CONTINUATION	$298,045
														Subtotal = $298,045

Issue Date FY: 2019 ( Subtotal = $298,098 )
2019	2019	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	4	5/17/2019	NON-COMPETING CONTINUATION	$298,098
														Subtotal = $298,098

Issue Date FY: 2018 ( Subtotal = $346,610 )
2018	2018	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	3	5/17/2018	NON-COMPETING CONTINUATION	$298,196
2018	2018	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	001	3	8/3/2018	SUPPLEMENT FOR EXPANSION	$48,414
														Subtotal = $346,610

Issue Date FY: 2017 ( Subtotal = $294,362 )
2017	2017	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	001	2	8/14/2017	NON-COMPETING CONTINUATION	$29,437
2017	2017	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL ST	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	2	5/16/2017	NON-COMPETING CONTINUATION	$264,925
														Subtotal = $294,362

Issue Date FY: 2016 ( Subtotal = $305,273 )
2016	2016	NORTHSHORE UNIVERSITY HEALTHSYSTEM	1301 CENTRAL STREET	EVANSTON	IL	60201	COOK	USA	Biomedical Research and Research Training	000	1	8/11/2016	NEW	$305,273
														Subtotal = $305,273

Grand Total All Awards = $2,616,253

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Developmental disruption of brain tissue oxygen regulation and deficiency of learning after neonatal anesthesia exposure

Award Number: R01GM112715

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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