Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion
Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion
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DOI：
10.1111/j.1471-4159.2011.07400.x
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发表时间：
2011-10-01
影响因子：
4.7
通讯作者：
Wang, Guolin
中科院分区：
文献类型：
--
作者：
Wang, Haiyun;Luo, Mengqiang;Wang, Guolin
我们先前报道，异丙酚(20 mg/kg/h)后处理对短暂性大脑中动脉闭塞大鼠具有急性(长达24小时)神经保护作用。在这项研究中，我们通过检查长期保护和探索涉及AMPA受体GluR2亚单位内化的潜在机制来扩展这些数据。缺血60min(再灌流4h)后给予异丙酚20 mg/kg/h。异丙酚后处理可减少脑梗塞体积，改善缺血/再灌流损伤所致的空间记忆缺陷(长达28天)。此外，异丙酚后处理促进了海马齿状回的神经发生，通过溴脱氧尿苷和神经元特异性核蛋白免疫荧光双重染色在再灌流后第28天进行检测。最后，异丙酚后处理增加AMPA受体GluR2亚单位的表面表达，从而抑制该部分的内化，直到卒中后28天。总之，我们的数据表明异丙酚后处理对大鼠局灶性脑缺血/再灌注损伤具有长期保护作用。此外，我们发现AMPA受体GluR2亚单位内化的抑制可能有助于这种长期的神经保护。
We previously reported that propofol (20 mg/kg/h) post-conditioning provided acute (up to 24 h) neuroprotection in rats with transient middle cerebral artery occlusion. In this study, we extend these data by examining long-term protection and exploring underlying mechanisms involving AMPA receptor GluR2 subunit internalization. Rats were treated with propofol 20 mg/kg/h after 60 min of occlusion (beginning of reperfusion for 4 h). Propofol post-conditioning reduced infarct volume and improved spatial memory deficiencies (up to 28 days) induced by ischemia/reperfusion injury. Additionally, Propofol post-conditioning promoted neurogenesis in the dentate gyrus of hippocampus, as measured by bromodeoxyuridine and neuron-specific nuclear protein immunofluorescence-double staining at day 28 after reperfusion. Finally, propofol post-conditioning increased the surface expression of AMPA receptor GluR2 subunit, thus inhibited the internalization of this part until 28 days after stroke. In conclusion, our data suggest that propofol post-conditioning provides long-term protection against focal cerebral ischemia/reperfusion injury in rats. Furthermore, we found that the inhibition of AMPA receptor GluR2 subunit internalization may contributed to this long-term neuroprotection.