Elsevier

Neuroscience

Volume 18, Issue 2, June 1986, Pages 417-436
Neuroscience

Reversible and irreversible neuronal damage caused by excitatory amino acid analogues in rat cerebellar slices

https://doi.org/10.1016/0306-4522(86)90163-6Get rights and content

Abstract

Slice preparations of the developing rat cerebellum were used to investigate the light and electron microscopic correlates of reversible and irreversible neuronal injury caused by the neurotoxic excitatory amino acid receptor agonists, kainate and N-methyl-d-aspartate. The slices were examined after various periods of exposure to the agonists (up to 30 min) with or without a 90 min recovery period in agonist-free medium. N-Methyl-d-aspartate (100 μM) caused necrosis of deep nuclear neurons and differentiating granule cells, the exposure times necessary to induce non-recoverable damage (leading to necrosis), being, respectively, 10 min and 20–30 min. Exposure periods of only 2–4 min with kainate (100 μM) were needed for Golgi cells to subsequently undergo necrosis. Other cell types (Purkinje, granule and deep nuclear neurons) were altered histologically by kainate but most recovered fully from 30 min exposures. Before the recovery period, the worst affected of these cells (deep nuclear neurons) displayed increased cytoplasmic and nuclear electron density and microvacuolation due to swelling of Golgi cisterns but little or no chromatin clumping or mitochondrial expansion. The neurons which were injured irreversibly by the agonists within 30 min displayed, near the time of lethal injury, increased cytoplasmic and nuclear electron lucency, marked focal aggregation of chromatin and swelling of Golgi apparatus. Mitochondrial swelling did not appear to precede lethal injury and even after exposure times sufficient, or more than sufficient, to lead to necrosis, large numbers of mitochondria remained in a condensed configuration. The significance of the histological changes is discussed and they are compared with those occurring in other pathological conditions. The time scales required for the receptor agonists to induce irreversible cellular lesions would be consistent with this being a process which is responsible for acute neuronal necrosis in the brain.

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Cited by (66)

  • Analyses of smooth endoplasmic reticulum of cerebellar parallel fibers in aging, ethanol-fed rats

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    Ethanol-related dilation of SER in parallel fibers has not been assessed. The plausibility of dilation of parallel fiber SER after chronic ethanol consumption, however, is supported by the fact that chronic (48 h) ethanol treatment up-regulates N-methyl-d-aspartate receptors (Chen et al., 1999) and dilation of granule neuron endoplasmic reticulum occurs after prolonged exposure of cerebellar slices to N-methyl-d-aspartate (Hajós et al., 1986). The finding of SER dilation in parallel fibers, taken with the previous report of SER dilation in Purkinje neuron dendrites (Dlugos & Pentney, 2000), would seem to indicate that SER dilation is an overall effect of ethanol on neuronal processes in the aging cerebellum.

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Permanent address: 1st Department of Anatomy, Semmelweis University Medical School, 1450 Tüzoltóutca 58, Budapest IX, Hungary.

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