Selegiline treatment after transient global ischemia in gerbils enhances the survival of CA1 pyramidal cells in the hippocampus.
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 14C-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.
Lahtinen
H
H
A.I. Virtanen Institute, University of Kuopio, Finland. hannele.lahtinen@helsinki.fi
Koistinaho
J
J
Kauppinen
R
R
Haapalinna
A
A
Keinänen
R
R
Sivenius
J
J
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D017403:In Situ Hybridization; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D012642:Selegiline