Hara H, Kato H, Onodera H, Kawagoe J, Kogure K
Department of Neurology, Tohuku University School of Medicine, Sendai, Japan.
Brain Res. 1992 Mar 6;574(1-2):26-32. doi: 10.1016/0006-8993(92)90795-b.
Changes in the binding of [3H]cyclic AMP as an indicator of particulate cyclic AMP-dependent protein kinase (AMP-DPK) binding activity following transient forebrain ischemia were studied in the gerbil using in vitro autoradiography. [3H]Cyclic AMP binding in the strata pyramidale and lacunosum-moleculare of the hippocampal CA1, the stratum pyramidale of the CA3, and the dentate gyrus decreased transiently in the early postischemic phase but then recovered. However, [3H]cyclic AMP binding in the strata pyramidale and radiatum of the CA1, the granular layer of the dentate gyrus, and the upper layer of the cortex decreased again 7 days after ischemia. In the CA4 subfield and the lower layer of the cortex, the binding showed no significant alterations after ischemia. Administration of pentobarbital prior to the induction of ischemia prevented the decrease in [3H]cyclic AMP binding in the CA1 subfield 6 h and 7 days after ischemia, and showed protective effects against neuronal death of the CA1 pyramidal cells 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield. Furthermore, postischemic reduction of [3H]cyclic AMP binding in the histologically intact cerebral cortex, CA3, and dentate gyrus may be the reflection of cellular dysfunction after energy failure.
利用体外放射自显影技术，在沙鼠身上研究了短暂性前脑缺血后，作为颗粒性环磷酸腺苷依赖性蛋白激酶（AMP-DPK）结合活性指标的[3H]环磷酸腺苷结合情况的变化。海马CA1区的锥体层和分子层、CA3区的锥体层以及齿状回中的[3H]环磷酸腺苷结合在缺血后早期短暂降低，但随后恢复。然而，缺血7天后，CA1区的锥体层和辐射层、齿状回的颗粒层以及皮质上层中的[3H]环磷酸腺苷结合再次降低。在CA4亚区和皮质下层，缺血后结合无明显变化。在缺血诱导前给予戊巴比妥可防止缺血后6小时和7天时CA1亚区[3H]环磷酸腺苷结合的降低，并对缺血7天后CA1锥体细胞的神经元死亡显示出保护作用。这些结果表明，细胞内信号转导的明显改变先于海马CA1亚区的神经元损伤。此外，组织学上完整的大脑皮质、CA3区和齿状回中缺血后[3H]环磷酸腺苷结合的减少可能是能量衰竭后细胞功能障碍的反映。
