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Pathogenesis of brain lesions caused by experimental epilepsy

Light- and electron-microscopic changes in the rat hippocampus following bicuculline-induced status epilepticus

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Summary

Status epilepticus with a duration of 1 or 2 h was induced in rats by i. v. injection of the GABA receptor blocking agent, bicuculline. Immediately there-after, or following a 2 h recovery period, the brains were fixed by vascular perfusion and processed for light and electron microscopy to characterize the type and distribution of morphological changes in the hippocampal formation.

In a previous study (Söderfeldt et al. 1981) astrocytic edema and wide-spread neuronal changes of two different kinds occurred in the fronto-parietal cortex of the same animals. Type 1 injured neurons were characterized by condensation of karyoplasm and cytoplasm (type 1a), which in some neurons became so intense that the nucleus could no longer be clearly discerned (type 1b). The type 2 injured neurons had slitformed cytoplasmic vacuoles chiefly caused by dilatation of the rough endoplasmic reticulum.

In the hippocampus the most conspicuous alteration was astrocytic edema which was most marked around the perikarya of pyramidal neurons in CA1-CA4 and subiculum. In the dentate gyrus the edema was less pronounced and, when present, affected particularly the hilar zone of the stratum granulosum. The nerve cell changes were less pronounced than in the cerebral cortex. The vast majority of the hippocampal pyramidal neurons in CA1-CA4 showed minor configurational and tinctorial abnormalities (incipient type 1a change). Severe nerve cell alterations (type 1b) were present but very rarely affected the pyramidal neurons of CA1-CA4 and subiculum, whereas in the dentate gyrus pyramidal basket neurons of stratum granulosum and pyramidal nerve cells in stratum polymorhe showed the severe type 1b changes. As compared with the frontoparietal cortex (Söderfeldt et al. 1981) the type 2 changes were extremely rare. In the early recovery period after 1 h of status epilepticus the astrocytic edema and the incipient type 1a changes had almost entirely disappeared, whereas a few condensed and dark-staining type 1b injured neurons remained.

Thus, in this model of status epilepticus the most marked response in the hippocampal formation is astrocytic edema in the layers where pyramidal perikarya are located. Incipient, mild nerve cell changes which appear to be reversible were frequent and widespread in the entire hippocampal formation.

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Authors and Affiliations

  1. Laboratory of Neuropathology, University of Uppsala, Uppsala, Sweden

    A. Atillo & Y. Olsson

  2. Laboratory for Experimental Brain Research, E-blocket, University Hospital, S-221 85, Lund, Sweden

    B. Söderfeldt & B. K. Siesjö

  3. Dept. of Pathology, University of Turku, Turku, Finland

    H. Kalimo

Authors
  1. A. Atillo
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  2. B. Söderfeldt
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  3. H. Kalimo
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  4. Y. Olsson
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  5. B. K. Siesjö
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Supported by grants from the Swedish Medical Research Council projects 12X-03020, 14X-263, from the US Public Health Service via NIH, from the Finnish Medical Research Council, and from Margarethahemmet Society

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Atillo, A., Söderfeldt, B., Kalimo, H. et al. Pathogenesis of brain lesions caused by experimental epilepsy. Acta Neuropathol 59, 11–24 (1983). https://doi.org/10.1007/BF00690312

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