Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin, Campus Virchow-Klinikum und Charité Campus Mitte, Charité Centrum 7 für Anästhesiologie, OP-Management und Intensivmedizin, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Brain Res. 2010 Jul 9;1343:14-9. doi: 10.1016/j.brainres.2010.04.081. Epub 2010 May 7.
Exposure to Gamma-aminobutyric-acid (GABA)(A)-receptor agonists and N-Methyl-D-Aspartate (NMDA)-antagonists has been demonstrated to induce neurodegeneration in newborn rats. Exogenous erythropoietin (EPO) protects against NMDA antagonist-mediated neuronal death. In this study we evaluated whether EPO is also effective in limiting neurodegeneration of the GABA(A)-mimetic agent propofol in newborn rats. 6 day old rats were randomized to one of four groups and treated with intraperitoneal applications of 3 x 30 mg/kg propofol at 0, 90 and 180 min, propofol in combination with 5000 IU/kg rEPO, propofol in combination with 20,000 IU/kg rEPO or sham injections of PAD II solution as controls. After 24h, brains of the animals were histopathologically examined and a summation score of degenerated cells was calculated for every brain. Propofol increased neuronal degeneration scores from 16,090+/-4336 to 28,860+/-6569 (p<0.01). This effect was completely abolished by low-dose rEPO (14,270+/-4542, p<0.001 versus propofol only; p>0.05 versus controls). In contrast, high-dose rEPO was not protective (23 930+/-8896, p>0.05 versus propofol only). Propofol may cause neuronal death in newborn rat brains, which is prevented by low-dose rEPO but not high-dose rEPO.
γ-氨基丁酸（GABA）（A）-受体激动剂和 N-甲基-D-天冬氨酸（NMDA）-拮抗剂的暴露已被证明可诱导新生大鼠的神经退行性变。外源性促红细胞生成素（EPO）可防止 NMDA 拮抗剂介导的神经元死亡。在这项研究中，我们评估了 EPO 是否也能有效限制新生大鼠 GABA（A）模拟物异丙酚引起的神经退行性变。6 天大的大鼠随机分为四组，分别接受腹腔注射 3×30mg/kg 异丙酚，0、90 和 180 分钟，异丙酚联合 5000IU/kg rEPO，异丙酚联合 20000IU/kg rEPO 或 sham 注射 PAD II 溶液作为对照。24 小时后，对动物的大脑进行组织病理学检查，并对每个大脑的退化细胞进行总和评分。异丙酚使神经元退化评分从 16090+/-4336 增加到 28860+/-6569（p<0.01）。低剂量 rEPO（14270+/-4542，与仅用异丙酚相比 p<0.001；与对照相比 p>0.05）完全消除了这种作用。相比之下，高剂量 rEPO 没有保护作用（23930+/-8896，与仅用异丙酚相比 p>0.05）。异丙酚可能导致新生大鼠大脑中的神经元死亡，低剂量 rEPO 可预防这种死亡，但高剂量 rEPO 不行。
