Otsubo K, Katayama Y, Terashi A
Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Nihon Ika Daigaku Zasshi. 1993 Aug;60(4):231-40. doi: 10.1272/jnms1923.60.231.
Glycerol and mannitol are used clinically as hyperosmolar agents for the treatment of brain edema. In the present study the effects of pre-ischemic treatment with glycerol or mannitol on delayed neuronal death in the gerbil hippocampal CA1 region were examined. In addition, the effects of post-ischemic treatment with glycerol were studied. Male Mongolian gerbils were subjected to transient forebrain ischemia by bilateral common carotid artery occlusion for 5 min. Skull and rectal temperatures were maintained at 36.5 +/- 0.5 degrees C from 30 min prior to occlusion through 60 min post-ischemia. In the pre-treatment study, glycerol (650 mg/kg or 1,300 mg/kg), mannitol (650 mg/kg or 1,300 mg/kg), or saline were administered intraperitoneally to the gerbils 30 min before ischemia. In the post-treatment study, 1,300 mg/kg glycerol was given immediately or 60 min after ischemia. Seven days after the ischemic episode, the brains were fixed and stained for histopathological analysis. Normal pyramidal cell counts per 1 mm length in CA1 (neuronal density, ND) were then assessed under a light microscope. ND in the sham-operated normal control group was 275.3 +/- 16.7 (mean +/- SD). In the pre-treatment study, ND in ischemic gerbils treated with saline was 14.8 +/- 5.0. ND in ischemic animals treated with glycerol (650 or 1,300 mg/kg) or mannitol (650 or 1,300 mg/kg) were 29.0 +/- 15.7, 68.2 +/- 56.7, 88.9 +/- 79.8 and 52.8 +/- 54.4 respectively. Both glycerol and mannitol, at either dose, significantly ameliorated ND. In the post-treatment study, ND in gerbils treated with saline or glycerol immediately after ischemia were 10.3 +/- 3.4 and 43.1 +/- 78.4, respectively, and 60 min after ischemia, 13.1 +/- 9.5 and 68.9 +/- 68.9, respectively. The ND in both post-treatment groups were not ameliorated significantly. These results indicate that pre-treatment with glycerol or mannitol has protective effects on delayed neuronal death in the gerbil hippocampal CA1 region, while post-treatment with glycerol does not produce any significant protection of CA1 neurons from transient ischemia.
甘油和甘露醇在临床上用作高渗剂治疗脑水肿。在本研究中，检测了缺血前用甘油或甘露醇预处理对沙鼠海马CA1区迟发性神经元死亡的影响。此外，还研究了缺血后用甘油治疗的效果。雄性蒙古沙鼠通过双侧颈总动脉闭塞5分钟造成短暂性前脑缺血。从闭塞前30分钟至缺血后60分钟，颅骨和直肠温度维持在36.5±0.5℃。在预处理研究中，在缺血前30分钟给沙鼠腹腔注射甘油（650mg/kg或1300mg/kg）、甘露醇（650mg/kg或1300mg/kg）或生理盐水。在治疗后研究中，在缺血后立即或60分钟给予1300mg/kg甘油。缺血发作7天后，将大脑固定并染色进行组织病理学分析。然后在光学显微镜下评估CA1区每1mm长度的正常锥体细胞计数（神经元密度，ND）。假手术正常对照组的ND为275.3±16.7（平均值±标准差）。在预处理研究中，用生理盐水治疗的缺血沙鼠的ND为14.8±5.0。用甘油（650或1300mg/kg）或甘露醇（650或1300mg/kg）治疗的缺血动物的ND分别为29.0±15.7、68.2±56.7、88.9±79.8和52.8±54.4。两种剂量的甘油和甘露醇均显著改善了ND。在治疗后研究中，缺血后立即用生理盐水或甘油治疗的沙鼠的ND分别为10.3±3.4和43.1±78.4，缺血后60分钟分别为13.1±9.5和68.9±68.9。两个治疗后组的ND均未得到显著改善。这些结果表明，用甘油或甘露醇预处理对沙鼠海马CA1区迟发性神经元死亡具有保护作用，而用甘油后处理对CA1神经元免受短暂性缺血没有产生任何显著的保护作用。
