Sheibani Negar, Grabowski Eric F, Schoenfeld David A, Whalen Michael J
Department of Pediatric Critical Care Medicine, The Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Crit Care Med. 2004 Nov;32(11):2274-8. doi: 10.1097/01.ccm.0000145998.11686.ed.
Granulocyte colony-stimulating factor has been used to reduce the risk of sepsis in patients with traumatic brain injury. However, granulocyte colony-stimulating factor exerts potent pro- and anti-inflammatory effects that could influence secondary injury, and outcome, after traumatic brain injury. Our objective was to determine the effect of granulocyte colony-stimulating factor on histopathologic, motor, and cognitive outcome after experimental traumatic brain injury in mice.
Experimental study.
Research laboratory at the Massachusetts General Hospital, Boston, MA.
Forty-eight adult male C57Bl/6 mice.
Mice (8 wks of age, n = 16/group) were administered granulocyte colony-stimulating factor or saline subcutaneously twice per day for 7 days after controlled cortical impact or sham injury (n = 16). Absolute neutrophil counts, motor function, Morris water maze performance, and lesion volume were determined after controlled cortical impact or sham injury.
At the time of controlled cortical impact, body weight, brain and body temperature, and systemic absolute neutrophil counts did not differ between groups. Compared with control, systemic absolute neutrophil count was increased more than ten-fold in granulocyte colony-stimulating factor-treated mice on posttrauma days 2 and 7 (p < .05, repeated-measures analysis of variance) but did not differ between groups by day 14. There were no differences between groups in tests of motor function or histopathologic outcome. However, compared with control, mice given granulocyte colony-stimulating factor had improved Morris water maze performance after controlled cortical impact (p < .05, repeated-measures analysis of variance) but not sham injury.
The data suggest a small beneficial effect of granulocyte colony-stimulating factor on functional outcome after traumatic brain injury in adult mice but do not show differences in histopathology or motor outcome between treated and control groups.
粒细胞集落刺激因子已被用于降低创伤性脑损伤患者发生败血症的风险。然而，粒细胞集落刺激因子具有强大的促炎和抗炎作用，可能会影响创伤性脑损伤后的继发性损伤及预后。我们的目的是确定粒细胞集落刺激因子对小鼠实验性创伤性脑损伤后组织病理学、运动和认知预后的影响。
实验研究。
马萨诸塞州波士顿市麻省总医院的研究实验室。
48只成年雄性C57Bl/6小鼠。
在可控皮质撞击或假手术损伤后（n = 16），小鼠（8周龄，n = 16/组）每天皮下注射粒细胞集落刺激因子或生理盐水两次，共7天。在可控皮质撞击或假手术损伤后测定绝对中性粒细胞计数、运动功能、莫里斯水迷宫表现和损伤体积。
在可控皮质撞击时，各组间体重、脑和体温以及全身绝对中性粒细胞计数无差异。与对照组相比，粒细胞集落刺激因子治疗的小鼠在创伤后第2天和第7天全身绝对中性粒细胞计数增加了十倍以上（p < 0.05，重复测量方差分析），但在第14天各组间无差异。各组在运动功能测试或组织病理学结果方面无差异。然而，与对照组相比，给予粒细胞集落刺激因子的小鼠在可控皮质撞击后莫里斯水迷宫表现有所改善（p < 0.05，重复测量方差分析），但假手术损伤后无改善。
数据表明粒细胞集落刺激因子对成年小鼠创伤性脑损伤后的功能预后有轻微有益作用，但未显示治疗组和对照组之间在组织病理学或运动预后方面存在差异。
