The effects of the 21-aminosteroid U-74389G on spatial orientation in rats after a cerebral oligemic episode and iron-induced oxidative stress

Christine Marcelle Heim, W. Kolasiewicz, K. H. Sontag

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oligemic episodes and increased iron concentration have both been proposed as being involved in neurodegenerative diseases. In animal models, a combination of both of these might therefore mimic the clinical pathology in humans. In rats, intrastriatal injections of ferric chloride, FeCl3, one week after a 60-minute oligemic episode, produced by bilateral clamping of the carotid arteries under pentobarbital anaesthesia (BCCA) impaired the animals' learning ability in a water maze task. Median adult rats, after intrastriatal 0.3 μg FeCl3, are impaired when challenged during the first three trial blocks, while after 0.06 μg FeCl3, an impairment is seen during the process of habituation to the challenge. Two-year-old animals do not show any learning effect at all after the combination of BCCA and intrastriatal FeCl3. Lazaroid U-74389G, a potent inhibitor of iron-induced lipid peroxidation, totally prevents the learning impairments in both median adult and aged animals, suggesting that iron-induced lipid peroxidation may be responsible for the late learning deficiencies. However, when U-74389G is applied one week after the oligemic episode but without the additional injection of iron, U-74389G on its own also impairs the animals' learning ability. The present animal model, when applied to clinical studies of lazaroids in humans, does seem able to give reliable information concerning the neuroprotective properties of such drugs.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalJournal of Neural Transmission
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2000

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Oxidative Stress
Iron
Learning
Aptitude
Lipid Peroxidation
Animal Models
Injections
Clinical Pathology
Pentobarbital
Carotid Arteries
Constriction
Neurodegenerative Diseases
Anesthesia
U 74389F
Water
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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abstract = "Oligemic episodes and increased iron concentration have both been proposed as being involved in neurodegenerative diseases. In animal models, a combination of both of these might therefore mimic the clinical pathology in humans. In rats, intrastriatal injections of ferric chloride, FeCl3, one week after a 60-minute oligemic episode, produced by bilateral clamping of the carotid arteries under pentobarbital anaesthesia (BCCA) impaired the animals' learning ability in a water maze task. Median adult rats, after intrastriatal 0.3 μg FeCl3, are impaired when challenged during the first three trial blocks, while after 0.06 μg FeCl3, an impairment is seen during the process of habituation to the challenge. Two-year-old animals do not show any learning effect at all after the combination of BCCA and intrastriatal FeCl3. Lazaroid U-74389G, a potent inhibitor of iron-induced lipid peroxidation, totally prevents the learning impairments in both median adult and aged animals, suggesting that iron-induced lipid peroxidation may be responsible for the late learning deficiencies. However, when U-74389G is applied one week after the oligemic episode but without the additional injection of iron, U-74389G on its own also impairs the animals' learning ability. The present animal model, when applied to clinical studies of lazaroids in humans, does seem able to give reliable information concerning the neuroprotective properties of such drugs.",
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The effects of the 21-aminosteroid U-74389G on spatial orientation in rats after a cerebral oligemic episode and iron-induced oxidative stress. / Heim, Christine Marcelle; Kolasiewicz, W.; Sontag, K. H.

In: Journal of Neural Transmission, Vol. 107, No. 1, 01.01.2000, p. 95-104.

Research output: Contribution to journalArticle

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