スナネズミ海馬における遅発性神経細胞壊死に対するglycerolおよびmannitolの保護効果について

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

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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.<BR>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°C from 30 min prior to occlusion through 60 min post-ischemia. In the pre-treatment study, glycerol (650mg/kg or 1, 300mg/kg), mannitol (650mg/kg or 1, 300mg/kg), or saline were administered intraperitoneally to the gerbils 30 min before ischemia. In the post-treatment study, 1, 300mg/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.<BR>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, 300mg/kg) or mannitol (650 or 1, 300mg/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.<BR>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.<BR>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.

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