The studies outlined in this proposal form a cohesive theme focused on ischemic injury and recovery mechanisms in perinatal hypoxia-ischemia. These projects arose as an outgrowth of the last cycle, but with new and exciting directions for the projects. We will now turn our attention to the long-term repair and recovery mechanisms. Our multi-disciplinary approach is maintained in this renewal with the human research project and three laboratory projects that all inform each other and are supported by two cores. The administrative core provides budgetary oversight, training and data management, while the technology core provides a central facility for both the human and laboratory studies for MR imaging and development as well as a repository for MRI development. In Project 1 """"""""White matter injury as predictor of outcome in neonatal brain injury"""""""", we plan to focus on the injury to white matter and to correlate the damage in major white matter pathways with neurodevelopmental outcome. We will utilize short echo 3D MR spectroscopic imaging (SEMRSI) to detect changes in metabolites relevant to the injury process, and we also propose to apply high angular resolution diffusion tensor imaging (HARDI) to detect small changes in water diffusion parameters (diffusivity and anisotropy). In Project 2 """"""""Role of Vascular Endothelial Growth Factor (VEGF) in recovery after ischemic neonatal brain injury"""""""", we will test whether VEGF plays a critical role in long-term recovery after neonatal stroke by promoting angiogenesis and neurogenesis. In Project 3 """"""""Effects of polyphenols on neonatal Hypoxia-ischemia (H-l) brain injury"""""""", we hypothesize that exposure to polyphenols from pomegranate juice as well as the specific polyphenol, resveratrol, will protect the neonatal brain against the acute effects of H-l. In addition, we hypothesize that delayed injury that occurs in the setting of neonatal H-l including axonal injury and regeneration will also be responsive to polyphenols. In Project 4 """"""""Tissue repair in two models of acute neonatal brain injury"""""""", we will focus on the repair process in two distinct models of neonatal brain injury - neonatal bacterial meningitis and transient middle cerebral artery occlusion. The two models share common features during the acute phase, such as tissue inflammation and apoptotic neuronal cell death;very little is known about the repair process in these models. These projects are all relevant to human disease as they will bring us closer to therapies for neonatal brain ischemia.

Public Health Relevance

TO PUBLIC HEALTH: Achieving these goals will ultimately result in improved care and outcome in encephalopathic neonates, and potential therapies aimed at the repair process after neonatal ischemic events.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS035902-14
Application #
8018597
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Bosetti, Francesca
Project Start
1998-04-01
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
14
Fiscal Year
2011
Total Cost
$1,085,488
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Gano, Dawn; Ho, Mai-Lan; Partridge, John Colin et al. (2016) Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns. J Pediatr 178:68-74
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Titomanlio, Luigi; Fernández-López, David; Manganozzi, Lucilla et al. (2015) Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models. Pediatr Neurol 52:566-84
Gano, Dawn; Andersen, Sarah K; Glass, Hannah C et al. (2015) Impaired cognitive performance in premature newborns with two or more surgeries prior to term-equivalent age. Pediatr Res 78:323-9
Gaynor, J William; Stopp, Christian; Wypij, David et al. (2015) Neurodevelopmental outcomes after cardiac surgery in infancy. Pediatrics 135:816-25

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