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MITOCHONDRIA, SUPEROXIDE & MNSOD IN A FETAL HYPOXIC CEREBRAL PALSY MODEL

Award Number: K08HD057307
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/06/2008
PERIOD OF PERFORMANCE END DATE: 08/31/2013

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MITOCHONDRIA, SUPEROXIDE & MNSOD IN A FETAL HYPOXIC CEREBRAL PALSY MODEL - DESCRIPTION (provided by applicant): Hypoxic-ischemic brain injury to fetuses results in stillbirths, neonatal death, cerebral palsy, mental retardation or learning disabilities. Hypoxia-ischemia in the fetus results in one of the highest indexes of burden of disease, if one considers mortality, lost years of life, loss of years of healthy life or the lifetime burden of caretakers. The long-term goal of our research group is to understand the mechanisms of brain injury and develop interventions that will ameliorate hypoxia-ischemic fetal brain injury. We have developed a clinically relevant model of acute placental insufficiency that results in a cerebral palsy phenotype in the newborn animals. Magnetic resonance imaging during the acute insult and the early reperfusion period predicts which animals will develop the cerebral palsy phenotype. This timing implicates oxidative stress and mitochondrial dysfunction as candidates for deciding cellular fate. One of the primary enzymes that removes superoxide one of the major sources of oxidative stress, is manganese superoxide dismutase which is found in the mitochondria The hypothesis is the level of mitochondrial dysfunction and superoxide accumulation are the initiators of brain cell injury. The level of manganese superoxide dismutase is crucial to for the ability of the mitochondrion to remove the superoxide before is causes damage. This proposal uses the predictive value of MRI and our animal model of cerebral palsy to look at mitochondrial dysfunction and superoxide at 30 minutes, 2 hours and 6 hours of reperfusion. It utilizes a unique approach to look directly at the brain cells in vitro after the insult before repair or ongoing injury cascades occur. It uses the unique tools of flow cytometry and cell sorting combined with molecular biology techniques. It will test antioxidant therapies in the clinical relevant animal model and if these are successful could lead to treatments that could decrease brain injury to newborn babies and decrease cerebral palsy, mental retardation or learning disabilities. Public Health Relevance: Lack of oxygen to the brain either before or just after a baby is born can result in severe brain damage or death of the baby. If the child survives one of the results can be cerebral palsy. This proposal aims to understand how lack of oxygen causes brain damage and will test potential treatments that could decrease the severity of brain damage and prevent the child from developing cerebral palsy.


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: 2012 ( Subtotal = $108,000 )
2012	2012	NORTHSHORE UNIVERSITY HEALTHSYSTEM RESEARCH INSTITUTE	1001 UNIVERSITY PLACE	EVANSTON	IL	60201	COOK	USA	Child Health and Human Development Extramural Research	000	5	7/26/2012	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2011 ( Subtotal = $108,000 )
2011	2011	NORTHSHORE UNIVERSITY HEALTHSYSTEM RESEARCH INSTITUTE	1001 UNIVERSITY PLACE	EVANSTON	IL	60201	COOK	USA	Child Health and Human Development Extramural Research	000	4	8/17/2011	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2010 ( Subtotal = $108,000 )
2010	2010	NORTHSHORE UNIVERSITY HEALTHSYSTEM RESEARCH INSTITUTE	1001 UNIVERSITY PLACE	EVANSTON	IL	60201	COOK	USA	Child Health and Human Development Extramural Research	000	3	8/28/2010	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2009 ( Subtotal = $108,000 )
2009	2009	NORTHSHORE UNIVERSITY HEALTHSYSTEM RESEARCH INSTITUTE	1001 UNIVERSITY PLACE	EVANSTON	IL	60201	COOK	USA	Child Health and Human Development Extramural Research	000	2	8/7/2009	NON-COMPETING CONTINUATION	$108,000
														Subtotal = $108,000

Issue Date FY: 2008 ( Subtotal = $108,000 )
2008	2008	EVANSTON NORTHWESTERN HEALTHCARE RESEARCH INSTITUTE	2650 RIDGE AVENUE	EVANSTON	IL	60201	COOK	USA	Child Health and Human Development Extramural Research	000	1	9/4/2008	NEW	$108,000
														Subtotal = $108,000

Grand Total All Awards = $540,000

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MITOCHONDRIA, SUPEROXIDE & MNSOD IN A FETAL HYPOXIC CEREBRAL PALSY MODEL

Award Number: K08HD057307

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/06/2008

PERIOD OF PERFORMANCE END DATE: 08/31/2013

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