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TIME-DEPENDENT CHANGES IN RESPIRATORY CONTROL AFTER PERINATAL HYPEROXIA

Award Number: R15HL083972
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2008
PERIOD OF PERFORMANCE END DATE: 05/31/2011

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TIME-DEPENDENT CHANGES IN RESPIRATORY CONTROL AFTER PERINATAL HYPEROXIA - DESCRIPTION (provided by applicant): Experiences during early life can have profound effects on the developing nervous system, including neural pathways responsible for the control of breathing. This project will use hyperoxia as a model to study environmental effects on the control of breathing as well as the body's response to perturbations in this critical homeostatic system. The hypoxic ventilatory response is attenuated in adult rats exposed to perinatal hyperoxia due to abnormal development of the carotid body and its afferent neurons, but little is known about respiratory control in these rats during the neonatal period. Although carotid body function is greatly diminished immediately after exposure to hyperoxia, preliminary data suggest that the respiratory control system compensates for this impairment, at least transiently, since hypoxic ventilatory responses appear normal in young rats. Indeed, it appears that hyperoxia elicits multiple forms of respiratory plasticity during development, some that are excitatory and some that are inhibitory, and that the balance among these influences changes over time. Ventilation measurements and neurophysiological techniques will be used to extend these novel observations over a range of postnatal ages and to explore the underlying mechanisms for time-dependent changes in respiratory control. The three specific aims of this project are: (1) to test the hypothesis that perinatal hyperoxia causes time-dependent changes in ventilation in rats, including an initial potentiation of the hypoxic ventilatory response followed by a persistent attenuation, (2) to test the hypothesis that these time- dependent changes in the hypoxic ventilatory response correlate to changes in carotid body function, and (3) to test the hypothesis that other components of the respiratory control system are upregulated after perinatal hyperoxia, thereby compensating for impaired carotid body development. If excitatory plasticity compensates for attenuated carotid body function in neonates, these mechanisms may ameliorate the adverse effects of impaired ventilatory chemoreflexes during critical periods of development. On the other hand, if hyperoxia potentiates chemoreceptor and ventilatory responses to hypoxia, this hypersensitivity could increase the risk of apneas and breathing instabilities. PUBLIC HEALTH RELEVANCE: The proposed experiments have particular relevance to infants that receive supplemental oxygen in neonatal intensive care units. Abnormal development of chemoreceptors and protective chemoreflexes may increase the risk of respiratory disorders and sudden infant death syndrome, a major cause of death in infants 1 month to 1 year of age. Therefore, it is critical to understand how environmental conditions in early life influence development of protective chemoreflexes.


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: 2010 ( Subtotal = $0 )
2010	2008	BATES COLLEGE	221 LANE HALL	LEWISTON	ME	04240	ANDROSCOGGIN	USA	Lung Diseases Research	000	1	11/9/2009	NEW	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $210,000 )
2008	2008	BATES COLLEGE	221 LANE HALL	LEWISTON	ME	04240	ANDROSCOGGIN	USA	Academic Research Enhancement Award	000	1	5/30/2008	NEW	$210,000
														Subtotal = $210,000

Grand Total All Awards = $210,000

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TIME-DEPENDENT CHANGES IN RESPIRATORY CONTROL AFTER PERINATAL HYPEROXIA

Award Number: R15HL083972

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2008

PERIOD OF PERFORMANCE END DATE: 05/31/2011

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