The Neonatal Brain Disorders Center is a multidisciplinary team of investigators collaborating to understand the impact of injury on brain development in the high risk newborn. Over the past 20 years, our research has been focused on the pathobiology of hypoxic-ischemic injury in the developing nervous system. This process differs markedly from that in the mature nervous system and through a series of investigations, both in vivo and in vitro, in animals and in humans, we have documented those differences. The immature brain is uniquely and exquisitely sensitive to oxidative stress that accounts for the cell death seen after hypoxia-ischemia. As in all neurological diseases, there are vulnerable regions of injury and these regions are damaged in an age-dependent manner. For example, in the premature brain, we see injury in the periventricular white matter that reflect damage to the developing oligodendrocytes, but we also have data to support that subplate neurons are involved as well . In the term baby, we see a different pattern of vulnerability, with damage to the deep gray nuclei and this pattern of vulnerability can be used to predict neurodevelopmental outcome later in life. Our human and laboratory projects address these issues.

Currently, we have three prospective human research studies ongoing to delineate injury patterns and identify prognostic factors that will determine neurodevelopmental outcome in babies with neonatal encephalopathy including:
BAMRI- "Brain Asphyxia MRI"- a study of the imaging characteristics of term newborn hypoxia-ischemia
PREMRI- "Preterm MRI" - a study of high risk preterm babies evaluating the effects of extreme prematurity on brain development
Cardiac MRI- a study of brain development in newborns with complex heart diseases We have studied over 200 preterm (PREMRI - Premature Asphyxia Magnetic Resonance Imaging) and 300 term (BAMRI -Brain Asphyxia Magnetic Resonance Imaging) and 50 Cardiac infants using state-of-the art magnetic resonance (MR) imaging modalities such as spectroscopy, diffusion tensor imaging, morphometry and perfusion mapping. There are also a number of clinical studies analyzing the effects of hypothermia in the treatment of newborn hypoxia-ischemia, the effects of seizures on the newborn brain, and the outcomes and risk factors for newborn stroke.

My laboratory primarily investigates the role of hypoxia- inducible genes using newborn animal models of stroke, hypoxia-ischemia and inflammation. We are investigating the role of postsynaptic density proteins and their relationship to the excitotoxic NMDA receptor, with a specific focus on the Src kinase family of proteins. We are also focusing on how the newborn brain responds to the injury in regard to repair. We are investigating the role of neurogenesis, angiogenesis and microglial activation after injury using targeted pharmacotherapies like growth factors (Epo, VEGF) to modulate the response. Our goal is to bring these pre-clinical studies to the bedside to improve outcome for newborns with brain injury.

Keywords: neonatal stroke, asphyxia, hypothermia, stem cells, treatment of ischemia.