Neuroprotection with erythropoietin administration following controlled cortical impact injury in rats
Neuroprotection with erythropoietin administration following controlled cortical impact injury in rats
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DOI：
10.1124/jpet.107.119628
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Robertson, Claudia
中科院分区：
文献类型：
--
作者：
Cherian, Leela;Clay Goodman, J.;Robertson, Claudia
本研究旨在确定促红细胞生成素（Epo）对创伤性脑损伤后脑血流量（CBF）、一氧化氮（NO）浓度和神经功能结局的影响。在一项实验中，通过测量平均动脉压、颅内压、使用激光多普勒血流仪的CBF和使用NO电极的脑组织NO浓度，在控制性皮质撞击损伤（CCII）后确定Epo的血流动力学效应。总共41只大鼠皮下给予Epo（5000 U/kg）或生理盐水。受伤前3天。在用生理盐水预处理的动物中，L-精氨酸而不是D-精氨酸给药导致组织NO浓度显著增加，并改善撞击部位的CBF。同样，在用Epo预处理的动物中，损伤后给予L-精氨酸而不是D-精氨酸增加脑组织NO浓度和CBF增加。在另一项实验中，74只大鼠接受CCII（3 mm变形，速度5 m/s），并给予生理盐水或Epo 5000 U/kg s.c.。伤后5 min、1 h、3 h、6 h、9 h或12 h。伤后2周，评估挫伤体积和海马CA 1和CA 3区存活神经元的细胞计数。在伤后5 min、1 h、3 h和6 h给予Epo，挫伤体积显著减小。海马CA 1、CA 3区神经元密度在伤后1、3、6 h均明显增加。这些数据证明了Epo在创伤性损伤中的神经保护作用，并且当在损伤后6小时内给予Epo时效果最佳。
This study was designed to determine the effect of erythropoietin (Epo) on cerebral blood flow (CBF), nitric oxide (NO) concentration, and neurological outcome after traumatic brain injury. In one experiment, the hemodynamic effects of Epo were determined after controlled cortical impact injury (CCII) by measuring mean arterial pressure, intracranial pressure, CBF using laser Doppler flowmetry, and brain tissue NO concentrations using an NO electrode. In total, 41 rats were given either Epo (5000 U/kg) or saline s.c. 3 days before injury. In animals pretreated with saline, L-arginine but not D-arginine administration resulted in a significant increase in tissue NO concentrations and an improvement in CBF at the impact site. Likewise, in animals pretreated with Epo, L-arginine but not D-arginine given postinjury increased brain tissue NO concentrations and increased CBF. In another experiment, 74 rats underwent CCII (3-mm deformation, velocity 5 m/s), and they were given saline or Epo 5000 U/kg s.c. at 5 min, 1 h, 3 h, 6 h, 9 h, or 12 h postinjury. The contusion volume and cell counts of viable neurons in the CA1 and CA3 regions of the hippocampus were assessed at 2 weeks postinjury. The contusion volume was significantly reduced at 5 min, 1 h, 3 h, and 6 h postinjury Epo administration. The neuron density in the CA1 and CA3 region of the hippocampus was increased at 1, 3, and 6 h after injury. These data demonstrate the neuroprotective effects of Epo in traumatic injury, and the effects are optimal when Epo is given within 6 h of injury.