H. Lahtinen et al., SELEGILINE TREATMENT AFTER TRANSIENT GLOBAL-ISCHEMIA IN GERBILS ENHANCES THE SURVIVAL OF CA1 PYRAMIDAL CELLS IN THE HIPPOCAMPUS, Brain research, 757(2), 1997, pp. 260-267
Selegiline (L-deprenyl) has shown neuroprotective effects in a variety
of degenerative processes, The present experiments were designed to t
est whether post-ischemia administered selegiline would alleviate dela
yed 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 aft
er 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 hybridizatio
n 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 signi
ficantly lower damage score (scale 0-3: 0, normal; 1, < 10% of the neu
rons damaged; 2, 10-50% damaged; 3, > 50% damaged) compared to the sal
ine-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 ex
pression of hsp70 mRNA in the CA1 pyramidal cell layer was strong stil
l 3 days after the ischemic insult but vanished by 7 days. Densitometr
ic 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 n
ot serve as a quantitative marker for CA1 neuronal injury in this mode
l. 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 del
ayed hippocampal neuronal death in gerbils when administered 2 h after
an ischemic insult.