Thromboxane synthetase inhibitor ameliorates delayed neuronal death in the CA1 subfield of the hippocampus after transient global ischemia in gerbils.
Thromboxane A2 accumulates in the hippocampus after global ischemia and may play a key role in postischemic hypoperfusion. Thromboxane synthetase inhibitor (OKY-046) inhibits the accumulation of thromboxane A2 and promotes prostacycline production. Therefore, we set out to determine whether the inhibition of thromboxane synthesis would ameriolate postischemic neuronal death. Three groups of six Mongolian gerbils were subjected to different treatments: untreated control, untreated ischemia, and treated ischemia. Immediately after forebrain ischemia, OKY-046 (10 mg/kg) was injected intraperitoneally into the treated group. After 7 days of survival, the histopathology of the brain was examined. Pyramidal cell density in the CA1 sector in the treated group was 147 +/- 70 nuclei/mm (mean +/- SD), which was significantly (p < 0.05) higher than than in the untreated group (33 +/- 10 (nuclei/mm). The findings were 231 +/- 7 nuclei/mm for the control group. No significant difference was seen in the profile of temporal muscle temperature before and after ischemia between the groups. Ultrastructurally, the vessels in the CAI sector showed lumen patency in the treated group, whereas occluded vessels with an extended perivascular space were observed in the untreated group. Thromboxane synthetase inhibitor thus partly ameliorates the selective vulnerability of the hippocampus after forebrain ischemia, suggesting that thromboxane A2 is involved in the development of delayed neuronal death, independently of any thermal effect.
Iijima
T
T
Department of Anesthesiology, School of Medicine, Kyorin University, Tokyo, Japan.
Sawa
H
H
Shiokawa
Y
Y
Saito
I
I
Ishii
H
H
Nakamura
Z
Z
Sankawa
H
H
D000818:Animals; D002452:Cell Count; D016923:Cell Death; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008689:Methacrylates / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D017966:Pyramidal Cells; D013696:Temperature; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel