Abstract
Background: Neuronal death following a hypoxic/ischaemic insult is thought to be caused by excitotoxicity, mediated via glutamate, the major excitatory neurotransmitter found in the central nervous system. ã-amino butyric acid (GABA) is the major inhibitory neurotransmitter in the brain. The GABA receptor is the target of many antiepileptic drugs used in neonates and infants. To date there are no studies examining the changes on the composition of the GABAA receptors by hypoxia in an animal model.
Methods: Eighteen 1-day old piglets were anaesthetised and ventilated. Following a standardised stabilisation period, the oxygen intake was decreased to 3 to 7%, in order to create a hypoxic insult as measured by suppressed EEG. The piglets were sacrificed 6 hours after the insult, the brain removed, sections taken and frozen. Subunits of the GABAA-receptor were quantified by Western Blot.
Results: There were no differences in birth weight, gender or postnatal age between the groups. Two central (hippocampus and thalamus) and two cortical regions (superior frontal and parietal cortex) were examined for the presence and changes of the GABAA subunits alpha 1, 2 and beta 2. At this short period of time following a hypoxic insult (6 hours), changes were evident in the alpha 2 and beta 2 subunits of the GABAA receptor in three regions.
Conclusion: Hypoxia alters subunits of the GABAA receptor; this may affect its inhibitory function and exacerbate hypoxic/ischaemic brain injury.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kecskes, Z., Dodd, P., Hendry, I. et al. 129 Hypoxia Alters Gabaa-Subunit Composition: Implications for Neural Rescue Therapy?. Pediatr Res 56, 486 (2004). https://doi.org/10.1203/00006450-200409000-00152
Issue Date:
DOI: https://doi.org/10.1203/00006450-200409000-00152