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A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Up-regulation of cerebral carbonic anhydrase by anoxic stress in piglets
Antal Nógrádi1, Ferenc Domoki, Rózsa Dégi
1Department of Ophthalmology, University of Szeged, H-6720 Szeged, Hungary.
Insights
Asphyxia in newborn piglets significantly increases carbonic anhydrase (CA) levels in the brain and retina. This rise in CA isoforms may help protect the neonatal central nervous system from damage.
Area of Science:
- Neuroscience
- Biochemistry
- Neonatal Physiology
Background:
- Resuscitation of asphyxiated infants can alter brain protein synthesis, impacting neurological outcomes.
- Rapid pH shifts in the brain during insufficient gas exchange highlight the role of carbonic anhydrase (CA) in pH buffering.
- Carbonic anhydrase (CA) is crucial for managing acute pH changes within the brain.
Purpose of the Study:
- To investigate the impact of asphyxia and re-ventilation on cerebral carbonic anhydrase (CA) isoforms (CA-II, CA-III, CA-IV) expression in newborn pigs.
- To determine if asphyxia influences the levels of CA-II, CA-III, and CA-IV in various brain regions and the retina.
Main Methods:
- Newborn piglets were subjected to 10 minutes of asphyxia followed by 2-4 hours of re-ventilation, with normoxic controls.
- Cerebral cortex, hippocampus, cerebellum, and retina were sampled for CA immunohistochemistry and immunoblotting.
- Quantification of CA immunoreactivity and protein levels for specific CA isoforms.
Main Results:
- Control piglets showed weak CA immunoreactivity (IR) except for moderate CA-II IR in specific cells (oligodendrocytes, astrocytes, Purkinje cells, Müller cells).
- Asphyxia followed by re-ventilation induced a marked increase in CA IR for all studied isoforms across all investigated cerebral regions and the retina after 4 hours.
- Immunoblotting confirmed elevated levels of all CA isoenzymes, with the most significant increase observed in pyramidal cells of the frontal cortex and hippocampus.
Conclusions:
- Asphyxia significantly upregulates carbonic anhydrase (CA) isoform expression in the neonatal piglet brain and retina.
- Increased CA levels following asphyxia likely represent a compensatory mechanism to protect the neonatal central nervous system (CNS) from pathological changes.
- These findings suggest a potential role for CA in mitigating neurological damage after perinatal asphyxia.
Abstract:
The resuscitation of asphyxiated babies is associated with changes in cerebral protein synthesis that can influence the neurological outcome. Insufficient gas exchange results in rapid shifts in extracellular and intracellular pH. Carbonic anhydrase (CA) plays an important role in buffering acute changes in pH in the brain. We investigated whether asphyxia/re-ventilation influences the expression of cerebral CA isoforms (CA-II, CA-III and CA-IV) in anaesthetized newborn pigs. The cerebral cortex, hippocampus, cerebellum and retina were sampled, and prepared for either CA immunohistochemistry or CA immunoblotting from piglets subjected to asphyxia (10 min) followed by 2-4 h of re-ventilation, and also from normoxic controls. The CA immunoreactivity (IR) of all the isoforms studied was weak in the controls, apart from staining of a few oligodendrocytes in the subcortical white matter, some astrocytes in the superficial layer of the cerebral cortex, the cerebellar Purkinje cells and the retinal Müller cells that possessed moderate CA-II IR. However, asphyxia induced a marked increase in the CA IR of all isoforms in all the cerebral regions investigated and the retina after 4 h of survival. The pyramidal cells of the frontal cortex and hippocampus displayed the most conspicuous increase in CA IR. Immunoblotting confirmed increased levels of all the CA isoenzymes. We conclude that raised CA levels after asphyxia may contribute to the compensatory mechanisms that protect against the pathological changes in the neonatal CNS.
