Katsura K, Rodriguez de Turco E B, Kristián T, Folbergrová J, Bazan N G, Siesjö B K
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
J Neurochem. 2000 Dec;75(6):2521-7. doi: 10.1046/j.1471-4159.2000.0752521.x.
Transient ischemia is known to lead to a long-lasting depression of cerebral metabolic rate and blood flow and to an attenuated metabolic and circulatory response to physiological stimuli. However, the corresponding responses to induced seizures are retained, demonstrating preserved metabolic and circulatory capacity. The objective of the present study was to explore how a preceding period of ischemia (15 min) alters the release of free fatty acids (FFAs) and diacylglycerides (DAGs), the formation of cyclic nucleotides, and the influx/efflux of Ca(2+), following intense neuronal stimulation. For that purpose, seizure activity was induced with bicuculline for 30 s or 5 min at 6 h after the ischemia. Extracellular Ca(2+) concentration (Ca(2+)(e)) was recorded, and the tissue was frozen in situ for measurements of levels of FFAs, DAGs, and cyclic nucleotides. Six hours after ischemia, the FFA concentrations were normalized, but there was a lowering of the content of 20:4 in the DAG fraction. Cyclic AMP levels returned to normal values, but cyclic GMP content was reduced. Seizures induced in postischemic animals showed similar changes in Ca(2+)(e), as well as in levels of FFAs, DAGs, and cyclic nucleotides, as did seizures induced in nonischemic control animals, with the exception of an attenuated rise in 20:4 content in the DAG fraction. We conclude that, at least in the neocortex, seizure-induced phospholipid hydrolysis and cyclic cAMP/cyclic GMP formation are not altered by a preceding period of ischemia, nor is there a change in the influx/efflux of Ca(2+) during seizure discharge or in associated spreading depression.
已知短暂性缺血会导致脑代谢率和血流量长期降低，并使对生理刺激的代谢和循环反应减弱。然而，对诱发性癫痫发作的相应反应得以保留，表明代谢和循环能力得以保存。本研究的目的是探讨在强烈神经元刺激后，前期缺血（15分钟）如何改变游离脂肪酸（FFA）和二酰甘油（DAG）的释放、环核苷酸的形成以及Ca(2+)的流入/流出。为此，在缺血后6小时用荷包牡丹碱诱导癫痫活动30秒或5分钟。记录细胞外Ca(2+)浓度（Ca(2+)(e)），并将组织原位冷冻以测量FFA、DAG和环核苷酸的水平。缺血6小时后，FFA浓度恢复正常，但DAG组分中20:4的含量降低。环磷酸腺苷（cAMP）水平恢复到正常值，但环磷酸鸟苷（cGMP）含量降低。缺血后动物诱发的癫痫发作在Ca(2+)(e)以及FFA、DAG和环核苷酸水平上显示出与非缺血对照动物诱发的癫痫发作相似的变化，只是DAG组分中20:4含量的升高有所减弱。我们得出结论，至少在新皮层中，前期缺血不会改变癫痫发作诱导的磷脂水解和环磷酸腺苷/环磷酸鸟苷的形成，在癫痫放电期间或相关的扩散性抑制中Ca(2+)的流入/流出也没有变化。
