Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats

Shenandoah Robinson, Kasia Petelenz, Qing Li, Mark L. Cohen, Anne DeChant, Nanor Tabrizi, Marik Bucek, David Lust, Robert H. Miller

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


In infants, a common consequence of systemic perinatal insults is disruption of neonatal brain development. Such insults can cause cerebral palsy, cognitive delay, epilepsy and other chronic neurologic deficits in children. The mechanisms underlying disruption of brain development after perinatal insults are poorly defined. To mimic human systemic insults, a transient prenatal hypoxic-ischemic insult model was developed in rodents. Ischemic animals showed reproducible histological lesions including oligodendrocyte loss, gliosis, and axonal disruption. Ischemic animals displayed persistent postnatal loss of oligodendrocyte lineage cells and cortical neurons, decreased cell proliferation, increased cell death, elevated pro-inflammatory cytokine levels, and impaired motor skills as young adults. Progressive ischemic intervals produced a graded pattern of injury. This systemic rodent prenatal hypoxic-ischemic insult accurately models human perinatal brain injury in several important criteria, including functional association of altered brain development with motor delay, and consequently provides novel insights into the pathogenesis of human perinatal brain insults.

Original languageEnglish (US)
Pages (from-to)568-581
Number of pages14
JournalNeurobiology of Disease
Issue number3
StatePublished - Apr 2005
Externally publishedYes


  • Cerebral palsy
  • Cytokines
  • Development
  • Ischemia
  • Oligodendrocyte
  • Periventricular leukomalacia
  • Prematurity
  • White matter lesions

ASJC Scopus subject areas

  • Neurology


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