Intraventricular administration of insulin and IGF-1 in transient forebrain ischemia.
A beneficial effect of insulin in reducing cerebral ischemic damage has been recently demonstrated, and a direct central mechanism of insulin action in cerebral ischemia has been proposed. To test the hypothesis that one of the neuroprotective mechanisms of insulin action involves a direct interaction with CNS tissue via a growth factor effect, a continuous intraventricular infusion of two doses of insulin and of insulin-like growth factor 1 (IGF-1) was given to fed Wistar rats subjected to 10 min, 15 s of transient forebrain ischemia. Quantitative neuropathology after 1-week survival showed that low-dose insulin (7 IU/rat/day; n = 10) reduced selective necrosis in the striatum (p = 0.015) and one level of the hippocampus (p = 0.023) as compared with animals infused with phosphate-buffered saline (200 microliters/rat/day; n = 8). IGF-1 (50 micrograms/rat/day; n = 8) significantly ameliorated hippocampal damage in four of the six hippocampal levels (p < 0.05). High-dose insulin infusion (23 IU/rat/day; n = 8) produced a robust reduction in cortical (p = 0.0108), striatal (p = 0.003), and hippocampal (p < 0.05) necrosis at all coronal levels. However, this high-dose insulin reduced the blood sugar significantly (p < 0.01), from 11.8 to 7.8 mM, probably by virtue of centrally administered insulin reaching the periphery. We conclude that insulin and IGF-1 offer a moderate, centrally mediated, neuroprotective effect, likely mediated at least in part via a growth factor mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
C Z
CZ
Neuroscience Research Group, University of Calgary, Alberta, Canada.
Auer
R N
RN
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D007334:Insulin-Like Growth Factor I