Dihydrolipoate Reduces Neuronal Injury after Cerebral Ischemia
| Autor: | Jochen H. M. Prehn, Jörg Nuglisch, Chourouk Karkoutly, Josef Krieglstein, Barbara Peruche |
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| Rok vydání: | 1992 |
| Předmět: |
Blood Glucose
Ischemia Glutamic Acid Hippocampus Blood Pressure Pharmacology Biology Nervous System Neuroprotection Body Temperature Brain Ischemia Lipid peroxidation Mice chemistry.chemical_compound Glutamates In vivo medicine Animals Neurons Thioctic Acid Cerebrum Rectum Thiourea Glutamate receptor Brain medicine.disease Rats Inbred F344 Rats medicine.anatomical_structure Neurology chemistry Neurology (clinical) Neuron Cardiology and Cardiovascular Medicine Neuroscience |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/jcbfm.1992.10 |
| Popis: | It has been shown in vitro that dihydrolipoate (dl-6,8-dithioloctanoic acid) has antioxidant activity against microsomal lipid peroxidation. We tested dihydrolipoate for its neuroprotective activity using models of hypoxic and excitotoxic neuronal damage in vitro and rodent models of cerebral ischemia in vivo. In vitro, neuronal damage was induced in primary neuronal cultures derived form 7-day-old chick embryo telencephalon by adding either 1 m M cyanide or 1 m M glutamate to the cultures. Cyanide-exposed and dihydrolipoate-treated (10−9–10−7 M) cultures showed an increased protein and ATP content compared with controls. The glutamate-exposed cultures treated with dihydrolipoate (10−7–10−5 M) showed a decreased number of damaged neurons. In vivo, dihydrolipoate treatment (50 and 100 mg/kg) reduced brain infarction after permanent middle cerebral artery occlusion in mice and rats. Dihydrolipoate treatment (50 and 100 mg/kg) could not ameliorate neuronal damage in the rat hippocampus or cortex caused by 10 min of forebrain ischemia. A comparable neuroprotection was obtained by using dimethylthiourea, both in vitro (10−7 and 10−6 M) and at a dose of 750 mg/kg in the focal ischemia models. Lipoate, the oxidized form of dihydrolipoate, failed to reduce neuronal injury in any model tested. We conclude that dihydrolipoate, similarly to dimethylthiourea, is able to protect neurons against ischemic damage by diminishing the accumulation of reactive oxygen species within the cerebral tissue. |
| Databáze: | OpenAIRE |
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