Transient hypoxemia chronically disrupts maturation of preterm fetal ovine subplate neuron arborization and activity

Evelyn McClendon, Daniel C. Shaver, Kiera Degener-O’Brien, Xi Gong, Thuan Nguyen, Anna Hoerder-Suabedissen, Zoltán Molnár, Claudia Mohr, Ben D. Richardson, David J. Rossi, Stephen A. Back

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Preterm infants are at risk for a broad spectrum of neurobehavioral disabilities associated with diffuse disturbances in cortical growth and development. During brain development, subplate neurons (SPNs) are a largely transient population that serves a critical role to establish functional cortical circuits. By dynamically integrating into developing cortical circuits, they assist in consolidation of intracortical and extracortical circuits. Although SPNs reside in close proximity to cerebral white matter, which is particularly vulnerable to oxidative stress, the susceptibility of SPNs remains controversial. We determined SPN responses to two common insults to the preterm brain: hypoxia-ischemia and hypoxia. We used a preterm fetal sheep model using both sexes that reproduces the spectrum of human cerebral injury and abnormal cortical growth. Unlike oligodendrocyte progenitors, SPNs displayed pronounced resistance to early or delayed cell death from hypoxia or hypoxia-ischemia. We thus explored an alternative hypothesis that these insults alter the maturational trajectory of SPNs. We used DiOlistic labeling to visualize the dendrites of SPNs selectively labeled for complexin-3. SPNs displayed reduced basal dendritic arbor complexity that was accompanied by chronic disturbances in SPN excitability and synaptic activity. SPN dysmaturation was significantly associated with the level of fetal hypoxemia and metabolic stress. Hence, despite the resistance of SPNs to insults that trigger white matter injury, transient hypoxemia disrupted SPN arborization and functional maturation during a critical window in cortical development. Strategies directed at limiting the duration or severity of hypoxemia during brain development may mitigate disturbances in cerebral growth and maturation related to SPN dysmaturation.

Original languageEnglish (US)
Pages (from-to)11912-11929
Number of pages18
JournalJournal of Neuroscience
Issue number49
StatePublished - Dec 6 2017


  • Anatomy and physiology
  • Dendrite
  • Hypoxia
  • Ischemia
  • Preterm brain injury
  • Subplate neurons

ASJC Scopus subject areas

  • Neuroscience(all)


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