|Budget Amount *help
¥7,500,000 (Direct Cost : ¥7,500,000)
Fiscal Year 1996 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥5,500,000 (Direct Cost : ¥5,500,000)
Effects of oxygen-18, a stable isotope of oxygen, on generation of oxygen free radicals in ischemic-reperfusion injury were investigated. Neuroprotective effects of oxygen-18 were examined in gerbil global brain ischemia. Ischemic neuronal damage were evaluated one week after a 5min bilateral carotid artery occlusion by an immunohistochemical reaction for microtubule-associated protein 2 (MAP2). In an oxygen-18 group, oxygen-18 gas was administered for 30min after ischemia, while in a control group, ordinary oxygen was administered. Comparing the neuronal density, i.e.the number of the surviving neurons per 1mm length of the CA1 region, there were no differences between the oxygen-18 and control groups. In the present study, neuroprotective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapper, were not demonstrated, either. Since the therapeutic effects of PBN are well-known, it is difficult to determine whether oxygen-18 has no neuroprotective effects from our results. Molecular orbital calculations did not evident distinctive features of oxygen-18, due to the complication of the calculation. One the other hand, a new spin tapping agent, 3,3,5-trimethyl-3-phenyl-1-pyrroline-N-oxide (Ph-M_3PO) was successfully synthesized, and it was documented that this compound effectively scavenged hydroxyl radicals. Moreover, it was also documented that pterin aldehyde, a xanthine oxidase inhibitor, has O_2^<.->scavenging activity. These newly synthesized and/or discovered spin trappers and free radical scavengers maay attenuate ischemicperfusion injury more effectively than conventional drugs.