Abstract 2035 Perinatal Brain Injury: Patterns and Mechanisms Platform, Tuesday, 5/4

Brain injury in the peripartum period causes a complex array of motor, sensory, cognitive, behavioral, and attentional deficits in survivors suggesting injury to multiple brain systems. The most well studied model of immature brain injury demonstrates severe injury in the distribution of the middle cerebral artery ipsilateral to the ligated common carotid. It is thought that injury occurs unilaterally in a distribution determined by the pattern of ischemia. We used silver-staining to demonstrate neuronal-cell body, axonal, and terminal degeneration in rat pup brains injured using the Vannucci model of neonatal *hypoxia-ischemia (H/I). We tested the hypothesis that brain damage is system preferential and has a distribution that follows connectivity patterns. In (n=2) brains analyzed 24, 48, 72 hours(h) following H/I, ipsilateral and contralateral forebrain damage was seen. Uninjured age-matched controls had a minimal basal level of argyrophilia consistent with developmental terminal degeneration and cell death. In H/I brains, abundant neuronal, axonal, and terminal degeneration is seen in ipsilateral and contralateral regions without common vascular supply. Primary motor/sensory systems are injured in a systems preferential manner. Columnar injury in the ipsilateral parasagittal cortex is accompanied by patchy ipsilateral striatal degeneration which varies in intensity with the degree of cortical injury. Specific regions which connect with cortex and striatum including ipsilateral ventrolateral thalamus, substantia nigra reticulata, ipsilateral cerebral pyramids, white matter axonal bundles crossing the midline, and layer V neurons in the contralateral cortex exhibit degeneration. Dying cells in the contralateral cortex exhibit light microscopic features of apoptosis more commonly than do those in the ipsilateral ischemic cortex. Degeneration is also seen in selective limbic system regions including the hippocampus, column of the fornix, mammilothalamic tract, anterior thalamic complex, and mammillary body. Contralateral cortical components of the limbic system also exhibit degeneration. Degeneration in motor, sensory, and limbic systems occurs rapidly following H/I, being present by 24h and without significant progression through 72h. This degeneration of specific brain regions following neonatal H/I reveals preferential vulnerability of brain systems based on neuronal connectivity rather than solely on vascular supply. Additionally, following H/I, the contralateral cortex is damaged in a manner consistent with injury secondary to degeneration of cortico-cortical projections. This pattern of injury is consistent with the complex clinical presentation of the multiply handicapped child following brain injury in the neonatal period.