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The distribution of hypoglycemic brain damage

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Summary

Rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. After recovery with glucose, they were allowed to wake up and survive for 1 week. Control rats were recovered at the stage of EEG slowing. After sub-serial sectioning, the number and distribution of dying neurons was assessed in each brain region. Acid fuchsin was found to stain moribund neurons a brilliant red.

Brains from control rats showed no dying neurons. From 10 to 60 min of cerebral isoelectricity, the number of dying neurons per brain correlated positively with the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min.

Neuronal necrosis was found in the major brain regions vulnerable to several different insults. However, within each region the damage was not distributed as observed in ischemia.

A superficial to deep gradient in the density of neuronal necrosis was seen in the cerebral cortex. More severe damage revealed a gradient in relation to the subjacent white matter as well. The caudatoputamen was involved more heavily near the white matter, and in more severely affected animals near the angle of the lateral ventricle. The hippocampus showed dense neuronal necrosis at the crest of the dentate gyrus and a gradient of increasing selective neuronal necrosis medially in CA1. The CA3 zone, while relatively resistant, showed neuronal necrosis in relation to the lateral ventricle in animals with hydrocephalus. Sharp demarcations between normal and damaged neuropil were found in the hippocampus. The periventricular amygdaloid nuclei showed damage closest to the lateral ventricles. The cerebellum was affected first near the foramina of Luschka, with damage occurring over the hemispheres in more severely affected animals. Purkinje cells were affected first, but basket cells were damaged as well. Rare necrotic neurons were seen in brain stem nuclei. The spinal cord showed necrosis of neurons in all areas of the gray matter. Infarction was not seen in this study.

The possibility is discussed that a neurotoxic substance borne in the tissue fluid and cerebrospinal fluid (CSF) contributes to the pathogenesis of neuronal necrosis in hypoglycemic brain damage.

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Authors and Affiliations

  1. Laboratory of Experimental Brain Research, University Hospital, S-221 85, Lund, Sweden

    R. N. Auer, T. Wieloch & B. K. Siesjö

  2. Neuropathology Laboratory, Dept. of Pathology, University of Uppsala, S-751 85, Uppsala, Sweden

    Y. Olsson

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  1. R. N. Auer
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  2. T. Wieloch
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  3. Y. Olsson
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  4. B. K. Siesjö
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Supported by the Swedish Medical Research Council (projects 12X-03020 and 14X-263) and the National Institutes of Health of the United States Public Health Service (grant no. 5 R01 NS07838)

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Auer, R.N., Wieloch, T., Olsson, Y. et al. The distribution of hypoglycemic brain damage. Acta Neuropathol 64, 177–191 (1984). https://doi.org/10.1007/BF00688108

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