[Protective effects of glycerol and mannitol on delayed neuronal death in the gerbil hippocampus].

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.