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

. 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 mgrkg 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 Ž 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 Ž . 1.73 " 0.18 and 2.41 " 0.16 mean " S.E.M., P s 0.0133 , respectively. A similar trend was found in animals after the 3-day treatment: Ž . 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 14 C-plastic standards showed that the intensity of the CA1a Ž . hsp70 signal on the 3rd day correlated negatively to the cell-damage score r sy0.72, 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 Ž . 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.