| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Intracellular recordings were made from CAl neurons of the rat hippocampal slice preparations. Superfusion with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization at 5 - 6 mi after onset. When oxygen and glucose were immediately reintroduced after the onset of the rapid depolarization, the membrane potential became persistently depolarized, reaching 0 mV after 5 mi (irreversible membrane dysfunction). When pretreated the slice preparation with phospholipase A2 inhibitor, para-BPB, which inhibits production of araachidonic acid, the membrane restored to the preexposure potential level with concentration dependent manner after the reintroduction. On the other hand, cyclooxygenase inhibitor, indomethacin, or lipoxygenase inhibitor, NDGA, did not restore the membrane potential. Pretreatment with 12- and 5-lipoxygenase inhibitor, dihydroxyphenyl ethanol or cycloxygenasel or 2 inhibitor, resveratrol or Dup-697, also did not show the neuroprotective effect. These results suggest that some products in the arachidonic acid metabolism protect the CAl neuron against the irreversible membrane dysfunction produced by in vitro ischemia or accelerate the membrane dysfunction. Pretreatment with prostaglandins (PGD2, PGEi, PGE2, PGF2u or PGI2 ligand, ciprostene) did not show the neuroprotective effect. On contrarily, pretreatment with free radical scavenger, edaravone or a-tocopherol, or thromboxane A2 synthase inhibitor, 0KY046 and CV4151, restore the membrane potential to the preexposure level after the reintroduction. These results suggest that the free radicals produce the irreversible membrane dysfunction. Free radicals may generate from the arachidonic acid metabolism with 5lipoxygenase and cycloxygenasel and 2.In addition, thromboxane A2 may accelerate the membrane dysfunction produced by in vitro ischemia.
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