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Relationship between putrescine content and density of ischemic cell damage in the brain of mongolian gerbils: effect of nimodipine and barbiturate

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Summary

Twenty mongolian gerbils were anesthetized (1.5% halothane) and severe forebrain ischemia was produced in 15 animals by occluding both common carotid arteries. After 5 min ischemia brains were recirculated spontaneously. Immediately after ischemia nimodipine (1.5 mg/kg) or pentobarbital (50 mg/kg) was injected intraperitoneally into five animals. Four days later animals were reanesthetized (1.5% halothane); the brains were frozen with liquid nitrogen and cut in a cryostat. Ten-micrometer-thick coronal cryostat sections were stained with cresyl violet to assess the extent of ischemic cell damage in the lateral striatum, the CA1-layer of the hippocampus, and the thalamus. In addition, tissue samples (about 4 mg each) were taken from the lateral striatum, CA1 layer of the hippocampus and the thalamus. Putrescine levels were measured in these samples using reversed-phase high performance liquid chromatography and fluorescence detection. Reversible cerebral ischemia produced a significant increase in putrescine in the lateral striatum (from 11.15±0.79 to 44.83±11.76 nmol/g,P≤0.05), the CA1 subfield of the hippocampus (from 11.27±0.64 to 41.80±3.62 nmol/g,P≤0.05) and less so in the thalamus (from 11.28±0.70 to 16.50±1.71 nmol/g). Both postischemic nimodipine and barbiturate treatment of animals markedly reduced this increase in the lateral striatum to 14.09±1.41 and 15.75±1.38 nmol/g, respectively (P≤0.05 cf. untreated animals), to 29.82±6.04 and 23.21±3.12 nmol/g in the CA1-subfield of the hippocampus (P≤0.05 barbiturate-treated cf. untreated animals), and to 11.92±1.37 and 11.76±0.64 in the thalamus (P<0.05 barbiturate-treated cf. untreated animals). Severe neuronal necroses were apparent in the lateral striatum in four out of five animals but in none of the nimodipine- or barbiturate-treated animals. In the CA1 subfield of the hippocampus the number of necrotic cells/mm stratum pyramidale amounted to 202.1±9.8, 141.9±4.2 and 78.0±33.4 in untreated, nimodipine- or barbiturate-treated animals, respectively (P≤0.05 barbiturate-treated cf. control animals). It is suggested that putrescine, produced during recirculation following ischemia, contributes to the manifestation of ischemic cell injury. Putrescine may thus be taken as a significant biochemical correlate of ischemic cell damage.

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Authors and Affiliations

  1. Abteilung für Experimentelle Neurologie, Max-Planck-Institut für Neurologische Forschung, Ostmerheimer Strasse 200, D-5000, Köln 91, Federal Republic of Germany

    W. Paschen, J. Hallmayer & G. Röhn

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  1. W. Paschen
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  2. J. Hallmayer
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  3. G. Röhn
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Supported by the Deutsche Forschungsgemeinschaft, grant Pa 266/2-4

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Paschen, W., Hallmayer, J. & Röhn, G. Relationship between putrescine content and density of ischemic cell damage in the brain of mongolian gerbils: effect of nimodipine and barbiturate. Acta Neuropathol 76, 388–394 (1988). https://doi.org/10.1007/BF00686976

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  • DOI: https://doi.org/10.1007/BF00686976

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