Cerebellar GABAA receptor alterations in hypoxic neonatal rats: Role of glucose, oxygen and epinephrine supplementation

• Published in: Neurochemistry international 2012-08, Vol.61 (3), p.302-309
• Main Authors: Anju, T.R., Anitha, M., Chinthu, R., Paulose, C.S.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain injury; Cerebellum; Epinephrine; Fundamental and applied biological sciences. Psychology; GABAA; gamma -Aminobutyric acid A receptors; gamma -Aminobutyric acid receptors; Glucose; Hypoxia; Neonatal hypoxia; Neonates; Neuroprotection; Neurotransmission; Oxygen; Resuscitation; Supplementation; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2012.05.023

[Display omitted] ► Neonatal hypoxia caused decreased GABAAα1, GABAAα5, GABAAγ3, GABAAδ receptor expression in the cerebellum. ► Glucose resuscitation, alone and with oxygen, reversed the altered GABAA receptor functions. ► Common clinical practice of 100% oxygen or epinephrine upset the GABAergic system. ► This highlights the importance of glucose supplementation in neonatal care to hypoxia. Hypoxia in neonates causes dysfunction of excitatory and inhibitory neurotransmission resulting in permanent brain damage. The present study is to understand the cerebellar GABAA receptor alterations and neuroprotective effect of glucose supplementation prior to current sequence of resuscitation – oxygen and epinephrine supplementation in hypoxic neonatal rats. Hypoxic insult caused a significant decrease in GABAA receptor number along with down regulated expression of GABAAα1, GABAAα5, GABAAδ and GABAAγ3 receptor subunits in the cerebellum which accounts for the respiratory inhibition. Hypoxic rats supplemented with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GABAA receptor subunits expression to near control. Glucose can reduce ATP-depletion-induced alterations in GABA receptors, thereby assisting in overcoming the neuronal damage caused by hypoxia. Resuscitation with oxygen alone and epinephrine was less effective in reversing the receptor alterations. The reduction in the GABAA receptors functional regulation during hypoxia plays an important role in cerebellar damage. Resuscitation with glucose alone and glucose with oxygenation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.