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‘Therapeutic window’ for multiple drug treatment of experimental cerebral ischemia in gerbils

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Abstract

The effects of the following drugs: nimodipine (1 mg/kg b. w., i. p.), 2-amino-5-phosphonovaleric acid (4mg/kg b.w., i.p.) and propentofylline (25mg/kg b.w., i.p.), administered (alone or in combination) at the end of 15 min bilateral ischemia in gerbils were evaluated on mitochondrial superoxide dismutase (SOD), glutathione reductase (GR), glucose-6 phosphate dehydrogenase (G6PD), monoamine oxidase (MAO) activities, and thiobarbituric acid reactive material (TBARM), and brain water content at 1 hour of reperfusion. The combined treatment virtually abolished early postischemic brain edema (4.1% v.s. 0.6%) and efficiently counteracted ischemia-induced changes [decreased SOD (79% v.s. 98%), GR (52% v.s. 105%) and MAO (25% v.s. 79%), and increased TBARM (198% v.s. 108%)]. The same combination of drugs administered 15 min before ischemia had a similar effect (e.g., reduced brain swelling and lipid peroxidation) as when given at the end of ischemia, whereas a limited or absent impact was seen when the drugs were given 15 min or 1 hour after ischemia, respectively. The data suggest that (post)ischemic brain swelling and mitochondrial dysfunction can be reduced by drugs which synchronously prevent processes induced in the early stages of reperfusion.

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Authors and Affiliations

  1. Stroke Branch, NINDS, NIH, Bldg. 36, Room 4B12, 20892, Bethesda, Maryland

    Danica B. Stanimirovic & Maria Spatz

  2. Institute of Biochemistry, School of Medicine, Belgrade

    Danica B. Stanimirovic, Dejan V. Micic, Marina Markovic & Bogomir B. Mrsulja

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  1. Danica B. Stanimirovic
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  2. Dejan V. Micic
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  3. Marina Markovic
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  4. Maria Spatz
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  5. Bogomir B. Mrsulja
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Stanimirovic, D.B., Micic, D.V., Markovic, M. et al. ‘Therapeutic window’ for multiple drug treatment of experimental cerebral ischemia in gerbils. Neurochem Res 19, 189–194 (1994). https://doi.org/10.1007/BF00966815

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