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Antioxidant treatme...
Antioxidant treatment protects striatal neurons against excitotoxic insults
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- Nakao, Naoyuki (författare)
- Lund University
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- Grasbon-Frodl, Eva Maria (författare)
- Lund University
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- Widner, H (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Regeneration in Movement Disorders,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Brundin, P (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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(creator_code:org_t)
- Elsevier BV, 1996
- 1996
- Engelska 16 s.
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 73:1, s. 185-200
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- It has been suggested that oxidative stress plays an important role in mediating excitotoxic neuronal death. We have therefore investigated the protective effects of antioxidants against excitotoxic injury in the rat on striatal neurons both in vitro and in vivo. In the first part of the study, we determined whether two different types of antioxidants, the spin trapping agent, alpha-phenyl-tert-butyl nitrone and an inhibitor of lipid peroxidation, U-83836E, could protect cultured striatal neurons against either hypoglycemic injury or N-methyl-D-aspartate-induced excitotoxicity. Dopamine- and cyclic AMP-regulated phosphoprotein, which is enriched in medium-sized spiny neurons, was chosen as a marker for striatal neurons. alpha-Phenyl-t-butyl nitrone and U-83836E both significantly reduced cell death induced by these insults as indicated by an increased number of surviving dopamine- and cyclic AMP-regulated phospho-protein-positive neurons. The two antioxidants also promoted the survival of cultured striatal neurons grown at low cell density under serum-free culture conditions. In an in vivo experiment systemically administered alpha-phenyl-t-butyl nitrone exerted neuroprotective effects in the rat striatum following injection of the excitotoxin quinolinic acid. Apomorphine-induced rotation tests revealed that alpha-phenyl-t-butyl nitrone-treated animals were significantly less asymmetric in their motor behavior than control rats. Treatment with alpha-phenyl-t-butyl nitrone significantly reduced the size of the quinolinic acid-induced striatal lesions, as assessed by the degree of sparing of dopamine- and cyclic AMP-regulated phospho-protein-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons, and of microtubule-associated protein-2-immunorective areas. Furthermore, lesion-induced morphological changes in the substantia nigra pars reticulate, i.e. loss of dopamine- and cyclic AMP-regulated phosphoprotein-positive afferent fibers and atrophic changes due to transsynaptic degeneration, were also less extensive in the alpha-phenyl-t-butyl nitrone-treated animals. The results support the hypothesis that oxygen-free radicals contribute to excitotoxic neuronal injury. The in vivo cytoprotective effects of alpha-phenyl-t-butyl nitrone against striatal excitotoxic lesions suggest that antioxidants could be used as potential neuroprotective agents in Huntington's disease, which has been suggested to involve excitotoxicity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Animals
- Antioxidants
- Cell Death
- Cell Survival
- Cells, Cultured
- Cyclic N-Oxides
- Dopamine and cAMP-Regulated Phosphoprotein 32
- Female
- Hypoglycemia
- Immunohistochemistry
- NADPH Dehydrogenase
- Neostriatum
- Nerve Degeneration
- Nerve Tissue Proteins
- Neurons
- Neurotoxins
- Nitrogen Oxides
- Phosphoproteins
- Quinolinic Acid
- Rats
- Rats, Sprague-Dawley
- Spin Labels
- Stereotyped Behavior
- Substantia Nigra
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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