title: Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia.
abstract: Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a "precritical period" of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic-ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia-ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development.
  
  
  CONCLUSIONS
  Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral, and language disabilities that limit academic achievement and well-being. Limited progress has been made to develop therapies that improve neurologic outcomes. The overall objective of this study is to understand the effect of early brain injury on activity-dependent brain development and cortical plasticity to develop new treatments that will optimize repair and recovery after brain injury.
authors: Departments of Pediatrics and.
authors: Sumudu
authors: S
authors: Ranasinghe
authors: Departments of Pediatrics and.
authors: Grace
authors: G
authors: Or
authors: Departments of Pediatrics and.
authors: Eric Y
authors: EY
authors: Wang
authors: Departments of Pediatrics and.
authors: Aiva
authors: A
authors: Ievins
authors: Departments of Pediatrics and.
authors: Merritt A
authors: MA
authors: McLean
authors: W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California San Francisco, San Francisco, California 94143, and.
authors: Cristopher M
authors: CM
authors: Niell
authors: Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada V6H 3V4.
authors: Vann
authors: V
authors: Chau
authors: Department of Pediatrics, University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia, Canada V6H 3V4.
authors: Peter K H
authors: PK
authors: Wong
authors: Departments of Pediatrics and Neurology and.
authors: Hannah C
authors: HC
authors: Glass
authors: Neurology and.
authors: Joseph
authors: J
authors: Sullivan
authors: Departments of Pediatrics and Neurology and patrick.mcquillen@ucsf.edu.
authors: Patrick S
authors: PS
authors: McQuillen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000254:growth & development* / Q000503:physiopathology*; D002657:Child Development / Q000502:physiology*; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007231:Infant, Newborn; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D011247:Pregnancy; D011446:Prospective Studies; D051381:Rats; D020318:Rats, Long-Evans; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
keywords: activity; hypoxia; ischemia; neonatal; plasticity; subplate