The co-treatments of vigabatrin and P2X receptor antagonists protect ischemic neuronal cell death in the gerbil hippocampus.
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.
Kim
Duk-Soo
DS
Department of Anatomy, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, South Korea.
Kwak
Sung-Eun
SE
Kim
Ji-Eun
JE
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000627:therapeutic use; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058469:Receptors, Purinergic P2X; D013498:Suramin / Q000627:therapeutic use; D013997:Time Factors; D020888:Vigabatrin / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000251:Adenosine Triphosphatases; D020888:Vigabatrin