Effect of hypoxia on the retina and superior colliculus of neonatal pigs

PLoS One. 2017 Apr 13;12(4):e0175301. doi: 10.1371/journal.pone.0175301. eCollection 2017.

Abstract

Purpose: To evaluate the effect of hypoxia on the neonatal pig retina and brain, we analysed the retinal ganglion cells (RGCs) and neurons in the superior colliculus, as well as the response of astrocytes in both these central nervous system (CNS) structures.

Methods: Newborn pigs were exposed to 120 minutes of hypoxia, induced by decreasing the inspiratory oxygen fraction (FiO2: 10-15%), followed by a reoxygenation period of 240 minutes (FiO2: 21-35%). RGCs were quantified using Brn3a, a specific nuclear marker for these cells, and apoptosis was assessed through the appearance of active caspase-3. A morphometric analysis of the cytoskeleton of astrocytes (identified with GFAP) was performed in both the retina and superior colliculus.

Results: Hypoxia produced no significant change in the RGCs, although, it did induce a 37.63% increase in the number of active caspase-3 positive cells in the superior colliculus. This increase was particularly evident in the superficial layers of the superior colliculus, where 56.93% of the cells were positive for active caspase-3. In addition, hypoxia induced changes in the morphology of the astrocytes in the superior colliculus but not in the retina.

Conclusions: Hypoxia in the neonatal pig does not affect the retina but it does affect more central structures in the brain, increasing the number of apoptotic cells in the superior colliculus and inducing changes in astrocyte morphology. This distinct sensibility to hypoxia may pave the way to design specific approaches to combat the effects of hypoxia in specific areas of the CNS.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis*
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Caspase 3 / biosynthesis
  • Hypoxia / metabolism*
  • Hypoxia / pathology
  • Hypoxia, Brain / metabolism*
  • Hypoxia, Brain / pathology
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology
  • Superior Colliculi / blood supply
  • Superior Colliculi / metabolism*
  • Superior Colliculi / pathology
  • Swine

Substances

  • Caspase 3

Grants and funding

We acknowledge the support of Retos-MINECO Fondos Fender (RTC-2016-48231) and Grupos Consolidados del Gobierno Vasco (IT437-10) to E.V.