Alterations in cortical GABAB receptors in neonatal rats exposed to hypoxic stress: role of glucose, oxygen, and epinephrine resuscitation
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Hypoxia in neonates can cause permanent brain damage by gene and receptor level alterations mediated through changes in neurotransmitters. The present study evaluated GABAB 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 GABAB receptors, GABAB 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 GABAB 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.
KeywordsGABAB Hypoxia Cerebral cortex Baclofen
This work was supported by the research grants from DBT, DST, ICMR, Govt. of India and KSCSTE, Govt. of Kerala to Dr. C. S. Paulose. T. R. Anju thanks Council of Scientific and Industrial Research for Senior Research Fellowship.
- 17.Wang GB, Wang XQ, Luo GX, He WF, Chen XW, Wu J, Bian XW (2007) Design of a multifunction medical experiment platform and its temperature regulation in cell in vitro culture. J Third Mil Med Univ 29:1289–1292Google Scholar
- 32.Dobbing J (1972) Undernutrition and the developing brain. The relevance of animal models to the human problem. Bibl Nutr Diet 17:35–46Google Scholar
- 43.Bandyopadhyay U, Das D, Ranajit K, Banerjee V (1999) Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci 77:658–666Google Scholar
- 45.Matharan TS, Laemmel E, Duranteau J, Vicaut E (2004) After hypoxia and glucose depletion causes reactive oxygen species production by mitochondria in HUVEC. Am J Physiol Regul Integr Comp Physiol 287:R1037–R1043Google Scholar
- 50.Binoy J, Nandhu MS, Paulose CS (2009) Dopamine D(1) and D(2) receptor functional down regulation in the cerebellum of hypoxic neonatal rats: neuroprotective role of glucose and oxygen, epinephrine resuscitation. Pharmacol Res. doi: 10.1016/j.phrs.2009.08.007