Araki T, Kato H, Shuto K, Itoyama Y
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Eur J Pharmacol. 1998 Aug 7;354(2-3):153-9. doi: 10.1016/s0014-2999(98)00457-9.
We investigated the post-ischemic change in [3H]L-N(G)-nitroarginine binding as a marker of nitric oxide (NO) synthase in the animal brain after transient global ischemia or transient focal ischemia. Transient global ischemia in gerbils was induced for 10 min followed by 1 h to 7 days of recirculation. Transient focal ischemia in rats was induced for 45 min followed by 3 days of recirculation. Following transient global ischemia, [3H]L-N(G)-nitroarginine binding showed a significant increase in the striatum (17-18%) and hippocampal CA1 sector (24%) at 48 and 24 h after recirculation, respectively. The hippocampal CA3 sector also showed a significant elevation (32-40%) in [3H]L-N(G)-nitroarginine binding at 24 and 48 h after global ischemia. Furthermore, the dentate gyrus showed a significant increase (30-32%) in [3H]L-N(G)-nitroarginine binding at 5, 24 and 48 h after global ischemia. Thereafter, a significant reduction in [3H]L-N(G)-nitroarginine binding was observed only in the dentate gyrus 7 days after recirculation. In contrast, [3H]L-N(G)-nitroarginine binding was unchanged in the thalamus throughout the recirculation periods. Histological analysis revealed that transient global ischemia caused severe damage or cellular damage in the striatum and the hippocampal CA1 sector. The hippocampal CA3 sector and thalamus were mildly damaged, whereas the dentate gyrus was morphologically intact. Following transient focal ischemia, a marked elevation (50-52%) in [3H]L-N(G)-nitroarginine binding was found in the regions of the ipsilateral striatum in which severe infarction occurred. Our findings suggest that [3H]L-N(G)-nitroarginine binding increases in the striatum and hippocampus after transient global ischemia or transient focal ischemia. This increase in [3H]L-N(G)-nitroarginine binding may play a pivotal role not only in the pathogenesis of ischemic brain damage, but also in the restoration of injury areas after cerebral ischemia.
我们研究了在短暂性全脑缺血或短暂性局灶性缺血后，动物脑中作为一氧化氮（NO）合酶标志物的[3H]L-N(G)-硝基精氨酸结合的缺血后变化。在沙鼠中诱导短暂性全脑缺血10分钟，随后再灌注1小时至7天。在大鼠中诱导短暂性局灶性缺血45分钟，随后再灌注3天。短暂性全脑缺血后，再灌注48小时和24小时时，纹状体中[3H]L-N(G)-硝基精氨酸结合分别显著增加（17 - 18%），海马CA1区增加（24%）。全脑缺血后24小时和48小时，海马CA3区[3H]L-N(G)-硝基精氨酸结合也显著升高（32 - 40%）。此外，齿状回在全脑缺血后5小时、24小时和48小时时，[3H]L-N(G)-硝基精氨酸结合显著增加（30 - 32%）。此后，仅在再灌注7天后的齿状回中观察到[3H]L-N(G)-硝基精氨酸结合显著减少。相比之下，在整个再灌注期间，丘脑中[3H]L-N(G)-硝基精氨酸结合没有变化。组织学分析显示，短暂性全脑缺血导致纹状体和海马CA1区严重损伤或细胞损伤。海马CA3区和丘脑轻度受损，而齿状回形态完整。短暂性局灶性缺血后，在发生严重梗死的同侧纹状体区域发现[3H]L-N(G)-硝基精氨酸结合显著升高（50 - 52%）。我们的研究结果表明，短暂性全脑缺血或短暂性局灶性缺血后，纹状体和海马中[3H]L-N(G)-硝基精氨酸结合增加。这种[3H]L-N(G)-硝基精氨酸结合的增加可能不仅在缺血性脑损伤的发病机制中起关键作用，而且在脑缺血后损伤区域的恢复中也起关键作用。
