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.