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Diabetologia

, Volume 39, Issue 2, pp 129–134 | Cite as

Hypoglycaemic brain damage: effect of a dihydropyridine calcium channel antagonist in rats

  • R. N. Auer
  • L. G. Anderson
Originals
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Summary

Hypoglycaemic brain damage consists of selective necrosis of cerebral neurons related to the extracellular release of excitatory amino acids. Neuronal excitatory amino acid receptors are activated and calcium channels are opened. The present investigation was designed to test the effectiveness of dihydropyridine blockade of voltage-sensitive calcium channels in hypoglycaemic brain damage. Sixty-four rats were given either high-dose nimodipine, consisting of an initial bolus of 300 Μg/kg nimodipine administered at the stage of EEG slowing (blood glucose levels of 1.0–1.5 mmol/l), followed by continuous intravenous nimodipine infusion at 1.5 Μg · kg−1 · min−1, low-dose nimodipine, consisting of an initial bolus of 30 Μg/kg at the time of EEG slowing, followed by 0.15 Μg · kg−1 · min−1, an equal volume of vehicle solution, or 154 mmol/l NaCl. Animals receiving either low- or high-dose nimodipine had higher mortality, and increased brain damage compared with controls. Examination of the perfusion-fixed brains 1 week after recovery with glucose revealed that quantitated neuronal necrosis was worsened by nimodipine in the hippocampus, caudate nucleus and cerebral cortex. The present results in profound hypoglycaemia (accompanied by a flat EEG) contrast with the beneficial effect of nimodipine in brain ischaemia.

Key words

Hypoglycaemia brain damage neuronal necrosis channel antagonist dihydropyridine 

Abbreviations

EAA

Excitatory amino acid

NMDA

N-methyl-d-aspartate

VSCC

voltage-sensitive calcium channels

ANOVA

analysis of variance

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • R. N. Auer
    • 1
  • L. G. Anderson
    • 2
  1. 1.Department of PathologyUniversity of CalgaryCalgaryCanada
  2. 2.Department of Pharmacology and TherapeuticsUniversity of CalgaryCalgaryCanada

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