Abstract
Previous studies in our laboratory demonstrated the alteration in the physical state of synaptosomal membrane lipids and proteins in ischemia/ reperfusion injury using selective spin labels and electron paramagnetic resonance spectroscopy [Hall et al. (1995) Neuroscience61, 84-89]. Since many investigations have provided evidence for free radical generation during ischemia/reperfusion injury, we investigated whether a free radical scavenger would prevent the membrane damage, in gerbils. Further, experiments to determine if a secondary effect of polyamine generation at 14 h reperfusion could be blocked by this free radical scavenger or by an inhibitor of ornithine decaryboxylase were also carried out. The alterations in synaptosomal membrane integrity observed during ischemia/reperfusion injury were selectively neutralized by treatment with the free radical spin trap N-tert-butyl-α-phenylnitrone or an inhibitor of ornithine decarboxylase, difluoromethylornithine. Administration of N-tert-butyl-α-phenylnitrone prior to ischemia totally abrogated both lipid and protein alterations observed at 1 and 14 h reperfusion. Pretreatment with difluoromethylornithine neutralized only the 14 h change in lipid label motion. Treatment with N-tert-butyl-α-phenylnitrone at 6 h post ischemia showed only a slight attenuation of the 14 h lipid effect and no change in the protein effect. Difluoromethylornithine treatment at 6 h post ischemia negated the 14 h ischemia/reperfusion injury-induced lipid effect and had no effect on the protein change. These data support previous suggestions that free radicals and polyamines play a critical role in neuronal damage and cell loss following ischemia/reperfusion injury and that the polyamine effect is dependent upon free radical generation during ischemia/reperfusion injury.
Original language | English |
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Pages (from-to) | 591-600 |
Number of pages | 10 |
Journal | Neuroscience |
Volume | 69 |
Issue number | 2 |
DOIs | |
State | Published - Nov 1995 |
Bibliographical note
Funding Information:Acknowledgements--This work was supported by a grant from NIH (AG-10836) and a research contract from Centaur Pharmaceuticals.
Keywords
- 2,2,6,6-tetramethyl-4-maleimidopiperidine-1-oxyl
- 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- DFMO
- EDTA
- EGTA
- EPR
- HEPES
- HWHH
- IRI
- MAL-6
- N-methyl-d-aspartate
- N-tert-butyl-α-phenylnitrone
- NMDA
- ODC
- PBN
- PMSF
- S-adenosylmethionine decarboxylase
- SAMDC
- W/W
- brain
- difluoromethylornithine
- electron paramagnetic resonance
- ethylenediaminetetra-acetate
- ethyleneglycoltetraacetic acid
- free radicals
- gerbil
- half width at half height of the low-field line of the 5-NS EPR spectrum
- ischemia reperfusion injury
- ornithine decarboxylase
- phenylmethylsulfonyl fluoride
- polyamines
- the ratio of the amplitudes of the weakly immobilized to the strongly immobilized components of the low-field line of the MAL-6 EPR spectrum
ASJC Scopus subject areas
- Neuroscience (all)