Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682022, Kerala, India.
Neurochem Int. 2012 Aug;61(3):302-9. doi: 10.1016/j.neuint.2012.05.023. Epub 2012 Jun 6.
Hypoxia in neonates causes dysfunction of excitatory and inhibitory neurotransmission resulting in permanent brain damage. The present study is to understand the cerebellar GABA(A) 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 GABA(A) receptor number along with down regulated expression of GABA(Aα1,) GABA(Aα5), GABA(Aδ) and GABA(Aγ3) 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 GABA(A) 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 GABA(A) 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.
新生儿缺氧会导致兴奋性和抑制性神经递质功能障碍，从而导致永久性脑损伤。本研究旨在了解小脑 GABA(A) 受体的改变，以及在缺氧新生大鼠目前的复苏顺序（氧和肾上腺素补充）之前补充葡萄糖的神经保护作用。缺氧损伤导致小脑 GABA(A) 受体数量显著减少，同时 GABA(Aα1)、GABA(Aα5)、GABA(Aδ)和 GABA(Aγ3)受体亚基的表达下调，这与呼吸抑制有关。单独给予葡萄糖和给予氧气的缺氧大鼠的受体改变以及 GABA(A)受体亚基表达的变化均恢复到接近对照水平。葡萄糖可以减少 ATP 耗竭诱导的 GABA 受体改变，从而有助于克服缺氧引起的神经元损伤。单独用氧和肾上腺素复苏对逆转受体改变的效果较差。在缺氧期间，GABA(A)受体功能调节的减少在小脑损伤中起重要作用。单独给予葡萄糖和给氧复苏缺氧新生大鼠有助于保护大脑免受严重缺氧损伤。
