Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.
J Neurochem. 2011 Oct;119(1):210-9. doi: 10.1111/j.1471-4159.2011.07400.x. Epub 2011 Aug 22.
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.
我们之前报道过，丙泊酚（20mg/kg/h）后处理可提供短暂性大脑中动脉闭塞大鼠的急性（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作用并探索涉及 AMPA 受体 GluR2 亚基内化的潜在机制来扩展这些数据。在闭塞 60 分钟后（再灌注开始后 4 小时），用丙泊酚 20mg/kg/h 处理大鼠。丙泊酚后处理可减少梗塞体积，并改善缺血/再灌注损伤引起的空间记忆缺陷（长达 28 天）。此外，丙泊酚后处理可促进再灌注后 28 天海马齿状回的神经发生，这可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来测量。最后，丙泊酚后处理增加了 AMPA 受体 GluR2 亚基的表面表达，从而抑制了该部分的内化，直到中风后 28 天。总之，我们的数据表明，丙泊酚后处理可为大鼠局灶性脑缺血/再灌注损伤提供长期保护作用。此外，我们发现抑制 AMPA 受体 GluR2 亚基内化可能有助于这种长期神经保护作用。
