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Severe Malaria And Risk to The Brain (SMART Brain)

Award Number: R01NS055349
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: 04/15/2008
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Severe Malaria And Risk to The Brain (SMART Brain) - PROJECT SUMMARY/ABSTRACT Cerebral malaria (CM) and severe malarial anemia (SMA), which together affect >1 million children annually, are associated with long-term neurodevelopmental impairment (NDI). Our data show that some systemic factors are associated with NDI in CM and SMA (e.g., endothelial dysregulation, acute kidney injury), but others are associated with NDI CM alone (e.g., inflammatory cytokines). Our findings suggest that both shared and unique systemic pathways contribute to NDI in CM vs. SMA. While our studies to date have advanced understanding of systemic pathways that may lead to NDI in children with CM or SMA, the central nervous system (CNS) pathways that contribute to NDI in children after CM or SMA remain unknown. In children with CM, the relationship of CNS findings to NDI has rarely been assessed, while in children with SMA, there is a paucity of CNS testing. Without data on how CNS pathways relate to NDI after CM or SMA, optimal interventions to prevent or mitigate NDI cannot be developed. The central hypotheses of this study are that the contribution of systemic factors to NDI in CM or SMA is mediated by CNS factors, and that the specific factors and relative contributions of factors differ in CM and SMA. The proposed study will leverage investment by Indiana University (IU) in an IU-Global Health Uganda Center for Child Neurodevelopment in Jinja, Uganda. IU will donate a Hyperfine mobile MRI and BrainAmp EEG to the Center, and provide training in MRI, EEG and TCD testing. The specific aims of this study are to: 1) identify CNS risk factors for neurodevelopment impairment (NDI) after CM vs. SMA; 2) establish systemic risk factors for NDI after CM vs. SMA; and 3) define the pathways by which systemic and CNS factors contribute to NDI after CM vs. SMA. We will conduct the study in a cohort of 620 children 6 months to 4 years of age (120 children with CM, 300 with SMA, 100 with uncomplicated malaria and 100 community children) who will be followed for 12 months after disease/ enrollment and have neurodevelopmental testing at 12-month follow-up. CNS pathways will be evaluated through bedside MRI testing with the Hyperfine Swoop MRI, quantitative EEG and evoked response potential testing, and transcranial Doppler ultrasound evaluation of cerebral blood flow patterns. Systemic pathways identified in prior studies as associated with brain injury, long-term neurodevelopment or both will be tested for reproducibility. Finally, established and novel statistical models will be used to identify systemic and CNS risk factors and mediation pathways for long-term NDI. We expect that unique systemic and CNS pathways will lead to NDI in CM compared to SMA. Identification of these pathways will allow for targeted interventions to prevent NDI in the millions of children with CM or SMA. The study will constitute a major advance in the understanding of the pathophysiology of brain injury and recovery in severe malaria, and provide critical new information on brain biology that will inform studies of other childhood CNS diseases.


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 = $862,047 )
2025	2025	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	17	3/26/2025	NON-COMPETING CONTINUATION	$862,047
2025	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	16	2/21/2025	COMPETING CONTINUATION	$17,391
2025	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	2/21/2025	NON-COMPETING CONTINUATION	-$15,196
2025	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	2/21/2025	SUPPLEMENT FOR EXPANSION	-$2,195
														Subtotal = $862,047

Issue Date FY: 2024 ( Subtotal = $1,041,597 )
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	7/26/2024	SUPPLEMENT FOR EXPANSION	$83,213
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	1/25/2024	COMPETING CONTINUATION	$958,384
2024	2024	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	16	9/5/2024	COMPETING CONTINUATION	$0
														Subtotal = $1,041,597

Issue Date FY: 2023 ( Subtotal = $570,519 )
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	2/6/2023	SUPPLEMENT FOR EXPANSION	$72,005
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	15	3/24/2023	NON-COMPETING CONTINUATION	$0
2023	2023	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	1/28/2023	NON-COMPETING CONTINUATION	$498,514
														Subtotal = $570,519

Issue Date FY: 2022 ( Subtotal = $474,555 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	1/10/2022	NON-COMPETING CONTINUATION	$427,100
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	6/22/2022	NON-COMPETING CONTINUATION	$47,455
														Subtotal = $474,555

Issue Date FY: 2021 ( Subtotal = $575,671 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	1/27/2021	NON-COMPETING CONTINUATION	$493,262
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	8/17/2021	SUPPLEMENT FOR EXPANSION	$82,409
														Subtotal = $575,671

Issue Date FY: 2020 ( Subtotal = $464,878 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	2/11/2020	NON-COMPETING CONTINUATION	$46,488
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	1/8/2020	NON-COMPETING CONTINUATION	$418,390
														Subtotal = $464,878

Issue Date FY: 2019 ( Subtotal = $537,648 )
2019	2019	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	1/21/2019	COMPETING CONTINUATION	$537,648
2019	2018	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	4/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $537,648

Issue Date FY: 2018 ( Subtotal = $553,469 )
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	4/27/2018	NON-COMPETING CONTINUATION	$55,347
2018	2018	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	12/27/2017	NON-COMPETING CONTINUATION	$498,122
														Subtotal = $553,469

Issue Date FY: 2017 ( Subtotal = $553,469 )
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	7/10/2017	NON-COMPETING CONTINUATION	$55,347
2017	2017	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/11/2017	NON-COMPETING CONTINUATION	$498,122
														Subtotal = $553,469

Issue Date FY: 2016 ( Subtotal = $553,469 )
2016	2016	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/16/2015	NON-COMPETING CONTINUATION	$498,122
2016	2016	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	1/27/2016	NON-COMPETING CONTINUATION	$55,347
														Subtotal = $553,469

Issue Date FY: 2015 ( Subtotal = $553,469 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	7/15/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$553,469
														Subtotal = $553,469

Issue Date FY: 2014 ( Subtotal = $561,279 )
2014	2014	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	9/21/2014	COMPETING CONTINUATION	$0
2014	2014	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	1/3/2014	COMPETING CONTINUATION	$561,279
2014	2012	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/31/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $561,279

Issue Date FY: 2012 ( Subtotal = $529,735 )
2012	2012	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/22/2012	NON-COMPETING CONTINUATION	$529,735
														Subtotal = $529,735

Issue Date FY: 2011 ( Subtotal = $542,514 )
2011	2011	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	7/29/2011	NON-COMPETING CONTINUATION	$12,231
2011	2011	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/2/2011	NON-COMPETING CONTINUATION	$530,283
														Subtotal = $542,514

Issue Date FY: 2010 ( Subtotal = $625,099 )
2010	2010	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/12/2010	NON-COMPETING CONTINUATION	$546,999
2010	2010	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	9/3/2010	SUPPLEMENT FOR EXPANSION	$78,100
														Subtotal = $625,099

Issue Date FY: 2009 ( Subtotal = $528,164 )
2009	2009	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/1/2009	NON-COMPETING CONTINUATION	$528,164
														Subtotal = $528,164

Grand Total All Awards = $10,089,478

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Severe Malaria And Risk to The Brain (SMART Brain)

Award Number: R01NS055349

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: 04/15/2008

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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