Neuroprotective effects of lipoxygenase inhibitors against ischemic injury in rat hippocampal slice cultures.
Using organotypic cultures of rat hippocampal slices, we investigated the possible involvement of arachidonate cascades in neuronal death following ischemic insult. Oxygen/glucose deprivation-induced neuronal damage was efficiently attenuated by various inhibitors of lipoxygenase, whereas cyclooxygenase inhibitors were less effective. Interestingly, 5- and 12-lipoxygenases are likely to separately mediate ischemic injury in the hippocampus. The present study will provide novel therapeutic targets for the development of neuroprotective agents.
Arai
K
K
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
Nishiyama
N
N
Matsuki
N
N
Ikegaya
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D000860:Hypoxia / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008084:Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D018696:Neuroprotective Agents; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose