Royl Georg, Balkaya Mustafa, Lehmann Sabrina, Lehnardt Seija, Stohlmann Katharina, Lindauer Ute, Endres Matthias, Dirnagl Ulrich, Meisel Andreas
Department of Experimental Neurology, Charité-Universitaetsmedizin, Berlin, Germany.
Brain Res. 2009 Apr 10;1265:148-57. doi: 10.1016/j.brainres.2009.01.061. Epub 2009 Feb 7.
Recent experimental studies in rodents suggest that treatment with inhibitors of phosphodiesterase type 5 (PDE5) (tadalafil, sildenafil, zaprinast) not only increases cerebral blood flow but also improves functional recovery after stroke. Here, we investigated in a mouse model of stroke the effects of vardenafil on survival, functional outcome and lesion size after experimental stroke. Mice were subjected to experimental stroke by occlusion of the middle cerebral artery (MCAO) for 45 min. A group of mice received vardenafil (twice 10 mg/kg body weight per day orally over 14 days) starting 3 h after MCAO. Control animals received the vehicle only. Survival, body weight, and behavior were monitored over 4 weeks and brain lesions were measured by T2-weighted MRI, hematoxylin/eosin -- as well as GFAP-staining of cryostat sections, subsequently. The mortality in MCAO-operated animals amounted to 45% until day 10 after stroke and no significant difference in survival between the vardenafil- and vehicle-treatment groups was observed. Compared to sham-operated animals, MCAO-operated mice from both treatment groups demonstrated a significant weight loss until day 5 and regained their body weight by day 14 after ischemia. There was no significant difference between the vardenafil and vehicle-treated MCAO groups. In behavioral studies (sucrose consumption and pole test), analyzing sensorimotor functions as well as a parameter of depression-like symptoms, we observed no significant effect of vardenafil treatment on functional recovery in our model of stroke. Although we observed a trend towards less hemispherical atrophy in the vardenafil compared to the vehicle-treated group four weeks after MCAO our data do not suggest a functionally relevant CNS-tissue protective or regenerative effect in murine stroke.
近期在啮齿动物身上进行的实验研究表明，用5型磷酸二酯酶（PDE5）抑制剂（他达拉非、西地那非、扎普司特）进行治疗不仅能增加脑血流量，还能改善中风后的功能恢复。在此，我们在中风小鼠模型中研究了伐地那非对实验性中风后存活情况、功能结局和损伤大小的影响。通过闭塞大脑中动脉（MCAO）45分钟使小鼠发生实验性中风。一组小鼠在MCAO后3小时开始接受伐地那非治疗（每天口服两次，每次10 mg/kg体重，持续14天）。对照动物仅接受溶剂。在4周内监测存活情况、体重和行为，随后通过T2加权磁共振成像、苏木精/伊红染色以及冰冻切片的胶质纤维酸性蛋白（GFAP）染色来测量脑损伤。直到中风后第10天，接受MCAO手术的动物死亡率达45%，未观察到伐地那非治疗组和溶剂治疗组在存活情况上有显著差异。与假手术动物相比，两个治疗组接受MCAO手术的小鼠在缺血后第5天体重均显著下降，并在第14天恢复体重。伐地那非治疗组和溶剂治疗的MCAO组之间无显著差异。在行为学研究（蔗糖消耗和杆试验）中，分析感觉运动功能以及类似抑郁症状的参数，我们观察到在我们的中风模型中伐地那非治疗对功能恢复无显著影响。尽管在MCAO后四周，我们观察到与溶剂治疗组相比，伐地那非组有半球萎缩减轻的趋势，但我们的数据并不表明在小鼠中风中有功能相关的中枢神经系统组织保护或再生作用。
