Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia-Ischemia.

Published

Journal Article

Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) in Sprague-Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants.

Full Text

Duke Authors

Cited Authors

  • Jantzie, LL; Corbett, CJ; Firl, DJ; Robinson, S

Published Date

  • September 2015

Published In

Volume / Issue

  • 25 / 9

Start / End Page

  • 2683 - 2695

PubMed ID

  • 24722771

Pubmed Central ID

  • 24722771

Electronic International Standard Serial Number (EISSN)

  • 1460-2199

International Standard Serial Number (ISSN)

  • 1047-3211

Digital Object Identifier (DOI)

  • 10.1093/cercor/bhu066

Language

  • eng