Dixon C Edward, Ma Xiecheng, Kline Anthony E, Yan Hong Q, Ferimer Howard, Kochanek Patrick M, Wisniewski Stephen R, Jenkins Larry W, Marion Donald W
Department of Neurological Surgery and Safar Center for Resuscitation Research, University of Pittsburgh, PA 15260, USA.
Crit Care Med. 2003 Aug;31(8):2222-7. doi: 10.1097/01.CCM.0000080493.04978.73.
To test the hypothesis that etomidate treatment improves functional, cognitive, and histologic outcome after experimental traumatic brain injury.
Controlled animal study.
University research laboratory.
Male Sprague-Dawley rats.
Traumatic brain injury was produced by controlled cortical impact injury (4 m/sec, 2.6 mm of tissue deformation). Etomidate (2 mg/kg) was administered intravenously immediately before injury (n = 13) or 5 mins after injury (n = 12). Additional rats received saline treatment 5 mins after injury (n = 12) or served as sham controls (n = 10).
Rats were evaluated on beam balance and beam walk tasks on postoperative days 1-5 and then trained in the Morris water maze on postoperative days 14-18. On day 28, the rats were killed, and hippocampal CA1 and CA3 neuron counts and cortical lesion volume were measured in histologic brain sections. Preinjury etomidate attenuated beam balance deficits, water maze deficits, hippocampal CA3 neuronal loss, and cortical tissue loss but did not attenuate beam walk deficits or hippocampal CA1 neuronal loss. Postinjury etomidate attenuated water maze deficits, but it did not affect any other outcome measure.
Administration of etomidate both before and after injury attenuates secondary injury resulting from traumatic brain injury, but the effect is more pronounced with pretreatment. The ineffectiveness of postinjury etomidate on motor and histologic tasks suggests a brief therapeutic treatment window in rats. However, the treatment window in humans is unknown. Lastly, postinjury etomidate did not exacerbate neurologic or histologic outcome.
验证依托咪酯治疗可改善实验性创伤性脑损伤后的功能、认知及组织学转归这一假说。
对照动物研究。
大学研究实验室。
雄性斯普拉格-道利大鼠。
通过控制性皮质撞击伤（4米/秒，2.6毫米组织变形）造成创伤性脑损伤。在损伤前即刻（n = 13）或损伤后5分钟（n = 12）静脉注射依托咪酯（2毫克/千克）。另外的大鼠在损伤后5分钟接受生理盐水治疗（n = 12）或作为假手术对照组（n = 10）。
在术后第1 - 5天对大鼠进行横梁平衡和横梁行走任务评估，然后在术后第14 - 18天对其进行莫里斯水迷宫训练。在第28天，处死大鼠，测量脑组织切片中的海马CA1和CA3神经元数量以及皮质损伤体积。损伤前给予依托咪酯可减轻横梁平衡缺陷、水迷宫缺陷以及海马CA3神经元丢失和皮质组织丢失，但不能减轻横梁行走缺陷或海马CA1神经元丢失。损伤后给予依托咪酯可减轻水迷宫缺陷，但不影响其他任何转归指标。
损伤前后给予依托咪酯均可减轻创伤性脑损伤导致的继发性损伤，但预处理的效果更显著。损伤后给予依托咪酯对运动和组织学任务无效，提示大鼠存在短暂的治疗窗口期。然而，人类的治疗窗口期尚不清楚。最后，损伤后给予依托咪酯并未加重神经或组织学转归。
