Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampus

被引:44
作者
Lahtinen, H
Koistinaho, J
Kauppinen, R
Haapalinna, A
Keinanen, R
Sivenius, J
机构
[1] UNIV KUOPIO, AI VIRTANEN INST, NMR RES GRP, FIN-70211 KUOPIO, FINLAND
[2] ORION PHARMA, ORION CORP FARMOS, TURKU, FINLAND
[3] UNIV KUOPIO, DEPT NEUROL & NEUROSCI, FIN-70211 KUOPIO, FINLAND
[4] KUOPIO UNIV HOSP, SF-70210 KUOPIO, FINLAND
基金
芬兰科学院; 英国医学研究理事会;
关键词
l-deprenyl; stroke; cerebral ischemia; neurodegeneration; neuronal rescue; hsp70; mRNA;
D O I
10.1016/S0006-8993(97)00227-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Selegiline (L-deprenyl) has shown neuroprotective effects in a variety of degenerative processes, The present experiments were designed to test whether post-ischemia administered selegiline would alleviate delayed neuronal death of the gerbil hippocampal pyramidal cells following transient global ischemia. Common carotid arteries were occluded for 5 min, Saline or selegiline, 0.25 mg/kg s.c., was administered 2 h after the ischemia followed by a daily injection for either 3 or 7 days. After decapitation, the delayed death of the hippocampal CA1 pyramidal cells was assessed using Nissl-stained sections. In situ hybridization was used to reveal the expression of hsp70 mRNA 1, 3 or 7 days after the ischemia. Animals treated with selegiline for 7 days showed significantly lower damage score (scale 0-3: 0, normal; 1, < 10% of the neurons damaged; 2, 10-50% damaged; 3, > 50% damaged) compared to the saline-treated animals 1.73 +/- 0.18 and 2.41 +/- 0.16 (mean +/- S.E.M., P = 0.0133), respectively. A similar trend was found in animals after the 3-day treatment: 1.68 +/- 0.32 vs. 2.06 +/- 0.25 (P > 0.5). The expression of hsp70 mRNA in the CA1 pyramidal cell layer was strong still 3 days after the ischemic insult but vanished by 7 days. Densitometric measurements using C-14-plastic standards showed that the intensity of the CA1a hsp70 signal on the 3rd day correlated negatively to the cell-damage score (r = -0.72, P < 0.001), suggesting that hsp70 does not serve as a quantitative marker for CA1 neuronal injury in this model. Instead, the hsp70 expression was associated with improved neuronal survival lasting often longer in selegiline-treated animals (P > 0.5). The results show that a low dose of selegiline can alleviate the delayed hippocampal neuronal death in gerbils when administered 2 h after an ischemic insult.
引用
收藏
页码:260 / 267
页数:8
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