Gáspárová Zdenka, Janega Pavol, Babál Pavel, Snirc Vladimír, Stolc Svorad, Mach Mojmír, Ujházy Eduard
Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
Neuro Endocrinol Lett. 2009;30(5):574-81.
The idea of neuroprotective therapy for ischaemic stroke is based on results from studies on experimental animal models of brain ischaemia demonstrating efficacy of many natural and synthetic agents. Contrary to positive conclusions with antioxidants from animal models, clinical experience failed to find neuroprotectants so efficient in human stroke, infarction, brain trauma, tissue preservation, etc. Thus new highly effective neuroprotective agents need to be discovered.
Effects of 10-day oral treatment with the new pyridoindole derivative, code SMe1EC2, was analysed in the model of ischaemia in vitro measured five days after oral treatment, with focus on neuronal function recovery. The responses were determined by extracellular recording from rat hippocampal slices. Further, effect of SMe1EC2, applied into the incubation medium before and during ischaemia in vitro, was studied on the oedema extent in neurons of the CA1 area.
Ten-day oral treatment of rats with SMe1EC2 at the doses 50 or 250 mg/kg resulted in improved resistance of hippocampal neurons to 6.5-min hypoxia/hypoglycaemia in vitro measured during reoxygenation, compared to untreated rats. Application of the drug tested into the incubation medium 30 min before and during 6-min hypoxia/hypoglycaemia resulted in reduction of oedema formation in the CA1 area compared to untreated slices exposed to ischaemia in vitro.
The current study confirmed the neuroprotective effect of the pyridoindole antioxidant SMe1EC2 on the level of recovery of neuronal function as well as on affection of morphological changes expressed by reduced oedema extent in the rat hippocampus under ischemic conditions in vitro.
缺血性脑卒中神经保护治疗的理念基于对脑缺血实验动物模型的研究结果，这些研究表明许多天然和合成药物具有疗效。与动物模型中抗氧化剂的阳性结论相反，临床经验未能发现神经保护剂在人类中风、梗死、脑外伤、组织保存等方面如此有效。因此，需要发现新的高效神经保护剂。
在口服治疗五天后，分析新型吡啶吲哚衍生物SMe1EC2进行10天口服治疗对体外缺血模型的影响，重点关注神经元功能恢复。通过大鼠海马切片的细胞外记录来确定反应。此外，研究了在体外缺血前和缺血期间将SMe1EC2应用于孵育培养基对CA1区神经元水肿程度的影响。
与未治疗的大鼠相比，以50或250mg/kg的剂量对大鼠进行10天的SMe1EC2口服治疗，可提高海马神经元在复氧期间对体外6.5分钟缺氧/低血糖的耐受性。在6分钟缺氧/低血糖前30分钟和期间将受试药物应用于孵育培养基中，与体外暴露于缺血的未治疗切片相比，可减少CA1区的水肿形成。
当前研究证实了吡啶吲哚抗氧化剂SMe1EC2在体外缺血条件下对大鼠海马神经元功能恢复水平以及对水肿程度降低所表达的形态学变化的影响方面具有神经保护作用。
