Kim Duk-Soo, Kwak Sung-Eun, Kim Ji-Eun, Won Moo Ho, Kang Tae-Cheon
Department of Anatomy, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea.
Brain Res. 2006 Nov 20;1120(1):151-60. doi: 10.1016/j.brainres.2006.08.057. Epub 2006 Sep 18.
During transient global ischemia, the excessive accumulation of intracellular Ca2+ induced by several episodes triggers delayed neuronal death within the vulnerable CA1 region of the hippocampus after ischemia-reperfusion insults. Although P2X receptors provide an additional source of Ca2+ entry, little data are available that these receptors could modulate the performance of the ischemic neuronal death. Therefore, we investigated the roles of the P2X receptor in the ischemic neuronal damage associated with various sequelae of transient ischemia, and the effects of their antagonist on the ischemic insults. As the results, ischemic insults increased P2X receptor expression in the gerbil hippocampus. Neither vigabatrin (VGB) nor P2X receptor antagonists (suramin, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid) protected against the delayed neuronal death in the CA1 region of the hippocampus after ischemia. However, the co-treatments of VGB and P2X receptor antagonists effectively prevent ischemia-induced neurodegeneration. Therefore, these findings suggest that blockade of the P2X receptor accompanied by activation of GABAergic inhibition may play an important role in the neuroprotection against ischemic insults.
在短暂性全脑缺血期间，几次发作所诱导的细胞内Ca2+过度蓄积会在缺血再灌注损伤后引发海马体易损CA1区域内的迟发性神经元死亡。尽管P2X受体是Ca2+进入细胞的另一个来源，但关于这些受体能否调节缺血性神经元死亡的研究数据很少。因此，我们研究了P2X受体在与短暂性缺血各种后遗症相关的缺血性神经元损伤中的作用，以及其拮抗剂对缺血性损伤的影响。结果显示，缺血性损伤会增加沙鼠海马体中P2X受体的表达。vigabatrin（VGB）和P2X受体拮抗剂（苏拉明、磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸）均不能预防缺血后海马体CA1区域的迟发性神经元死亡。然而，VGB与P2X受体拮抗剂联合治疗可有效预防缺血诱导的神经变性。因此，这些发现表明，P2X受体的阻断伴随着GABA能抑制的激活可能在抗缺血性损伤的神经保护中起重要作用。
