Rischke R, Rami A, Bachmann U, Rabié A, Krieglstein J
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Ketzerbach, Marburg, BRD.
Pharmacology. 1992;45(3):142-53. doi: 10.1159/000138992.
The local cerebral glucose utilization (CMRglc) in the damaged rat hippocampal CA1 subfield increases 7 days after 10 min of cerebral ischemia. We have used the N-methyl-D-aspartate antagonist (NMDA antagonist) ketamine in rats 7 days after sham operation or cerebral ischemia to determine whether the elevated postischemic CMRglc of the CA1 subfield is due to long-lasting hyperexcitation of surviving or injured neurons, or, alternatively, to the metabolism of other cell types. The autoradiographic data were interpreted with the aid of histochemical analysis of the postischemic hippocampal cell changes. Anesthetic doses of ketamine significantly reduced the CMRglc in the CA1 strata oriens, pyramidale and radiatum of sham-operated rats, while the postischemic increases in CMRglc in these hippocampal CA1 strata were not affected by ketamine. In addition, there were ketamine-induced increases in the CMRglc of the CA1 stratum lacunosum moleculare of both sham-operated and postischemic rats. The immunoreactivity of the microtubule-associated protein 2 (MAP2), a postsynaptic protein marker, was decreased markedly in the CA1 subfield in postischemic rats, while the presynaptic protein marker, synaptophysin, remained the same in sham-operated and postischemic rats. The glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes raised markedly in the ischemically damaged CA1 subfield. Although it could be demonstrated that presynaptic terminals remain intact in the postischemic damaged CA1 subfield, the lacking ketamine effect on CA1 pyramidal neurons indicated that the increase in CMRglc in this brain area is not due to postsynaptic neural hyperexcitation, but probably has to be attributed to astrocytes activated by neuronal damage.
在大鼠大脑缺血10分钟后7天，受损海马CA1亚区的局部脑葡萄糖利用率（CMRglc）升高。我们在假手术或脑缺血7天后的大鼠中使用N-甲基-D-天冬氨酸拮抗剂（NMDA拮抗剂）氯胺酮，以确定CA1亚区缺血后CMRglc升高是由于存活或受损神经元的长期过度兴奋，还是由于其他细胞类型的代谢。通过对缺血后海马细胞变化的组织化学分析辅助解读放射自显影数据。麻醉剂量的氯胺酮显著降低了假手术大鼠CA1区的原层、锥体层和辐射层的CMRglc，而这些海马CA1层缺血后的CMRglc升高不受氯胺酮影响。此外，氯胺酮使假手术和缺血后大鼠的CA1分子层隙状层的CMRglc均升高。缺血后大鼠CA1亚区中突触后蛋白标记物微管相关蛋白2（MAP2）的免疫反应性显著降低，而突触前蛋白标记物突触素在假手术和缺血后大鼠中保持不变。星形胶质细胞的胶质纤维酸性蛋白（GFAP）免疫反应性在缺血损伤的CA1亚区显著升高。尽管可以证明缺血后受损的CA1亚区中突触前终末保持完整，但氯胺酮对CA1锥体神经元缺乏作用表明该脑区CMRglc的升高不是由于突触后神经的过度兴奋，而可能归因于神经元损伤激活的星形胶质细胞。
