The co-treatments of vigabatrin and P 2X receptor antagonists protect ischemic neuronal cell death in the gerbil hippocampus

Abstract

During transient global ischemia, the excessive accumulation of intracellular Ca 2+ induced by several episodes triggers delayed neuronal death within the vulnerable CA1 region of the hippocampus after ischemia–reperfusion insults. Although P 2X receptors provide an additional source of Ca 2+ entry, little data are available that these receptors could modulate the performance of the ischemic neuronal death. Therefore, we investigated the roles of the P 2X 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 P 2X receptor expression in the gerbil hippocampus. Neither vigabatrin (VGB) nor P 2X 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 P 2X receptor antagonists effectively prevent ischemia-induced neurodegeneration. Therefore, these findings suggest that blockade of the P 2X receptor accompanied by activation of GABAergic inhibition may play an important role in the neuroprotection against ischemic insults.