Xu Zhenfeng, Jiang Ju, Ford Gregory, Ford Byron D
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Biochem Biophys Res Commun. 2004 Sep 17;322(2):440-6. doi: 10.1016/j.bbrc.2004.07.149.
Recent work from our laboratory demonstrated that the expression neuregulin-1 in neurons was induced in the ischemic penumbra by focal stroke in the rat. Here, we show that a single intravascular injection of neuregulin-1beta (approximately 2.5 ng/kg) reduced cortical infarct volume by >98% when given immediately before middle cereral artery occlusion. Subcortical infarct volume was reduced by approximately 40%. Analysis of DNA fragmentation in brain tissues indicated that neuregulin-1 blocked apoptosis in cortical neurons in the penumbra. Neuregulin-1 prevented macrophage/microglial infiltration and astrocytic activation following focal ischemia. The neuroprotective effect of neuregulin-1 was also associated with a suppression of interleukin-1beta mRNA levels. These data suggest that neuregulin-1 protects neurons from delayed, ischemia-induced apoptotic cell death in the cortex by inhibiting pro-inflammatory responses. Neuregulins represent a novel, potent neuroprotective strategy that has potential therapeutic value in treating individuals after acute ischemic stroke.
我们实验室最近的研究表明，大鼠局灶性中风可诱导缺血半暗带神经元中神经调节蛋白-1的表达。在此，我们发现，在大脑中动脉闭塞前立即进行单次血管内注射神经调节蛋白-1β（约2.5 ng/kg），可使皮质梗死体积减少>98%。皮质下梗死体积减少约40%。对脑组织中DNA片段化的分析表明，神经调节蛋白-1可阻止半暗带皮质神经元的凋亡。神经调节蛋白-1可防止局灶性缺血后巨噬细胞/小胶质细胞浸润和星形细胞活化。神经调节蛋白-1的神经保护作用还与白细胞介素-1β mRNA水平的抑制有关。这些数据表明，神经调节蛋白-1通过抑制促炎反应，保护神经元免受皮质中延迟性缺血诱导的凋亡细胞死亡。神经调节蛋白代表了一种新型、有效的神经保护策略，在治疗急性缺血性中风后的个体方面具有潜在的治疗价值。
