Very preterm birth may result in neurodevelopmental handicap. This impairment of the normal acquisition of cognitive and motor skills is secondary to disruption of the appropriate sequencing of developmental cues, or genomic control mechanisms, during 24 through 30 weeks of gestation and results in abnormalities of neuronal metabolism, cytoskeletal processing, synaptic density, and receptor type. During this critical period of development, intraventricular hemorrhage will further perturb the intrinsic genetic timetable of the developing cerebral cortex. Intraventricular hemorrhage (IVH) occurs in over 45% of preterm neonates of < 1500 g birth weight and represents a major cause of mental retardation, seizures and motor handicaps in this population.
The first aim of this exploratory neonatal brain research grant is the development of animal models in which our hypotheses concerning very preterm birth-induced alterations in neuronal glucose metabolism and glutamate turnover, cytoskeletal processing, synaptic density and receptor type and the influence of a model for IVH on these measures may be tested. The second overall aim is to correlate these models with clinical studies of cerebral magnetic resonance imaging (MRI) and MRI determination of regional function-mediated cerebral blood flow as a marker for metabolic activity in very preterm infants who have been identified as having suffered IVH without parenchymal involvement. Gestational-aged matched infants with no evidence for IVH will serve as control subjects. Serial studies will be performed on both groups at 36 weeks postconceptional age and throughout the first 6 months after term and alterations in cerebral structure and regional function-mediated cerebral blood flow will be correlated with longterm neurodevelopmental testing. IVH is believed attributable to alterations in cerebral blood flow to the immature germinal matrix microvasculature; the risk period for IVH is the first 4 - 5 postnatal days and appears independent of gestational age. Our third goal in our attempt to prevent brain injury in the preterm infant will therefore be the investigation of the cellular and molecular bases of the perinatal induction of germinal matrix microvascular maturation for the perinatal prevention of IVH. Our longterm aim is to utilize the information grained from these studies to identify specific alternations in the expected genetic developmental timetable of cerebral development and test intervention strategies to promote normal cortical development.
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