Uno H, Kobayashi H, Handa Y, Kabuto M, Kubota T
Department of Neurosurgery, Fukui Medical University, Japan.
Acta Neurochir (Wien). 1999;141(3):287-94. doi: 10.1007/s007010050300.
To clarify the relation between neuronal protection against ischaemia and calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity, we investigated temporal alterations of the kinase activity in the hippocampus after transient forebrain ischaemia under neuroprotective conditions, employing the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrain ischaemia was 214.7 +/- 25.8/mm (mean +/- S.D.), and did not differ from the control significantly; however, it decreased to 11.7 +/- 4.2/mm at 7 days after the ischaemia. The neuronal density at 7 days after the ischaemia was 185.1 +/- 18.5 under the hypothermic conditions, 128.7 +/- 19.6 with the brief ischaemic pretreatment, 65.0 +/- 13.4 with administration of MK-801, and 20.5 +/- 4.2 with the repetitive hyperthermic pretreatment, respectively. The Ca2+/calmodulin-dependent activity of CaM kinase II in the hippocampal cytosolic fraction was decreased to 47.5% of the control value at 2 hours after the ischaemia, when CA1 neuronal death was not observed. In contrast, the activity was 98.8% of the control under the hypothermic conditions, 91.4% with the brief ischaemic pretreatment, 71.2% with administration of MK-801, and 47.9% with the repetitive hyperthermic pretreatment, respectively. These results indicated that the preservation of the Ca2+/calmodulin-dependent activity of cytosolic CaM kinase II after ischaemia parallelled the neuroprotective effect in the gerbil hippocampus. Thus, it is suggested that the preservation of the activity may be involved in the mechanism of neuronal protection against ischaemia.
为了阐明神经元对缺血的保护作用与钙/钙调蛋白依赖性蛋白激酶II（CaM激酶II）活性之间的关系，我们采用沙鼠双侧颈动脉闭塞模型，在神经保护条件下研究了短暂性前脑缺血后海马中该激酶活性的时间变化。在前脑缺血5分钟后2小时，海马CA1区神经元密度为214.7±25.8/mm（平均值±标准差），与对照组无显著差异；然而，缺血后7天时，该密度降至11.7±4.2/mm。缺血后7天时，低温条件下神经元密度为185.1±18.5，短暂缺血预处理后为128.7±19.6，给予MK-801后为65.0±13.4，重复高温预处理后为20.5±4.2。缺血后2小时，海马细胞溶质部分中CaM激酶II的Ca2+/钙调蛋白依赖性活性降至对照值的47.5%，此时未观察到CA1神经元死亡。相比之下，低温条件下该活性为对照的98.8%，短暂缺血预处理后为91.4%，给予MK-801后为71.2%，重复高温预处理后为47.9%。这些结果表明，缺血后细胞溶质CaM激酶II的Ca2+/钙调蛋白依赖性活性的保留与沙鼠海马中的神经保护作用平行。因此，提示该活性的保留可能参与了神经元对缺血的保护机制。
