Bednar Martin M
Pfizer Inc, Pfizer Global Research and Development, 50 Pequot Avenue, MS 8260-2604, New London, CT 06320, USA.
Curr Opin Investig Drugs. 2008 Jul;9(7):754-9.
The structural underpinning responsible for neuroplasticity and neurorestoration under physiological and pathophysiological conditions is only beginning to be elucidated. It is evident that life-long neurogenesis occurs in the human brain, with experimental data supporting its upregulation following an insult (eg, stroke) and/or in response to pharmacological therapy. Sildenafil, a PDE5 inhibitor currently marketed for the treatment of erectile dysfunction, enhances neurorestoration in rat models of stroke, as measured by neurogenesis, synaptogenesis and angiogenesis. This neurorestorative effect is associated with improved outcome despite no observed effect on brain infarct size. This neurorestorative effect has also been observed in both young and old animals, and is demonstrable even if therapy is initiated 1 week post-stroke. The extended therapeutic window and novel mechanism of action of neurorestorative therapies, such as sildenafil, warrant further investigation for the treatment of stroke.
在生理和病理生理条件下，负责神经可塑性和神经修复的结构基础才刚刚开始被阐明。显然，人类大脑中会发生终身性神经发生，实验数据支持在受到损伤（如中风）后和/或对药物治疗产生反应时其上调。西地那非是一种目前用于治疗勃起功能障碍的磷酸二酯酶5（PDE5）抑制剂，通过神经发生、突触形成和血管生成来衡量，它可增强中风大鼠模型中的神经修复。尽管未观察到对脑梗死大小有影响，但这种神经修复作用与改善的结果相关。在年轻和老年动物中均观察到了这种神经修复作用，即使在中风后1周开始治疗也可得到证实。神经修复疗法（如西地那非）的延长治疗窗口和新作用机制值得进一步研究用于中风治疗。
