Alterations in cortical GABAB receptors in neonatal rats exposed to hypoxic stress: role of glucose, oxygen, and epinephrine resuscitation.
Hypoxia in neonates can cause permanent brain damage by gene and receptor level alterations mediated through changes in neurotransmitters. The present study evaluated GABA(B) receptor alterations, gene expression changes in glutamate decarboxylase and hypoxia-inducible factor 1A in the cerebral cortex of hypoxic neonatal rats and the resuscitation groups with glucose, oxygen, and epinephrine. Under hypoxic stress, a significant decrease in total GABA and GABA(B) receptors, GABA(B) and GAD gene expression was observed in the cerebral cortex, which accounts for the respiratory inhibition. Hypoxia-inducible factor 1A was upregulated under hypoxia to maintain body homeostasis. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD and HIF-1A to near control. Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation, which helps in encountering hypoxia. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations. Thus, our study suggests that reduction in the GABA(B) receptors functional regulation during hypoxia plays an important role in cortical damage. Resuscitation with glucose alone and glucose and oxygen to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.
Anju
T R
TR
Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
Abraham
Pretty Mary
PM
Antony
Sherin
S
Paulose
C S
CS
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism*; D004837:Epinephrine / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage*; D000860:Hypoxia / Q000378:metabolism*; D010102:Oxygen Inhalation Therapy; D016133:Polymerase Chain Reaction; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*
D018080:Receptors, GABA-B; D005947:Glucose; D004837:Epinephrine
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