Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
Neurosci Res. 2013 Feb;75(2):160-6. doi: 10.1016/j.neures.2012.12.002. Epub 2012 Dec 29.
Ischemic neuron death is presumably caused by excitotoxicity. Here, we studied whether ischemia impaired astrocytes and GABAergic neurons to exacerbate glutamate-dependent neural excitotoxicity by electrophysiologically recording these nerve cells in cortical slices. Our results showed that ischemia impaired the activity of glutamate-transporters (Glu-T) on the astrocytes, as well as the ability of firing spikes and the response to excitatory synaptic inputs on GABAergic neurons. The impairments of glutamate reuptakes and GABAergic neurons led to the imbalance between excitation and inhibition toward neural excitotoxicity. When explored the protection of nerve cells from ischemia, we found that the ischemic impairments of astrocytes and GABAergic cells were prevented by 3,5-DHPG, an agonist for type-I/V of metabotropic glutamate receptors (mGluR). The activation of mGluR1,5 is likely a potential therapeutic strategy to prevent nervous tissues from excitotoxicity by reducing the impairment of the astrocytes and GABAergic neurons during the early stage of ischemia.
缺血性神经元死亡可能是由兴奋性毒性引起的。在这里，我们通过在皮质切片上电生理记录这些神经细胞，研究了缺血是否会损害星形胶质细胞和 GABA 能神经元，从而加剧谷氨酸依赖性神经兴奋性毒性。我们的结果表明，缺血损害了星形胶质细胞上的谷氨酸转运体 (Glu-T) 的活性，以及 GABA 能神经元产生尖峰和对兴奋性突触输入的反应的能力。谷氨酸再摄取和 GABA 能神经元的损伤导致兴奋和抑制之间的失衡，从而导致神经兴奋性毒性。当探索神经细胞免受缺血的保护时，我们发现，3,5-DHPG（I/V 型代谢型谷氨酸受体 (mGluR) 的激动剂）可预防星形胶质细胞和 GABA 能细胞的缺血损伤。mGluR1,5 的激活可能是一种潜在的治疗策略，通过减少缺血早期星形胶质细胞和 GABA 能神经元的损伤，来防止神经组织发生兴奋性毒性。
