Summary
Status epilepticus was induced in rats by the GABA receptor blocking agent, bicuculline, during artificial ventilation and with closely monitored physiologic parameters. After 1 or 2 h of status epilepticus the brains were fixed by perfusion with glutaraldehyde and processed for light and electron microscopy.
In the cerebral cortex two different types of changes were present, i.e., nerve cell injuries and status spongiosus. Type 1 injured neurons, mainly in the areas of most marked sponginess (layer 3), displayed progressive condensation of both karyo-and cytoplasm. In the most advanced stages the nucleus could no longer be distinguished from the cytoplasm in the light microscope, and vacuoles of apparent Golgi cisterna origin appeared in the darkly stained cytoplasm. This type of injured neurons comprised 41 and 56% of the cortical neurons after 1 or 2 h of status epilepticus, respectively.
Seven to 9% of the neurons showed another type of injury (type 2). They were mainly located in the deeper cortical layers, and showed slit-formed cytoplasmic vacuoles chiefly due to swelling of the endoplasmic reticulum including the nuclear envelope.
Marked sponginess of the cortex developed principally in layer 3 and it spread into deeper layers with longer duration of status epilepticus, but the outermost layers retained a compact structure. As judged by electron microscopy, the sponginess resulted mainly from swelling of astrocytes and their processes causing both perivascular and perineuronal vacuolation.
The structural changes observed are considered to be caused by astrocytic and to a lesser extent intraneuronal edema related to the seizure activity. Although the exact pathogenetic mechanisms are not known, our findings indicate that hypoxia-ischemia is not a major determinant of the tissue damage observed.
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The study was supported by grants from the Swedish Medical Research Council (project nos. 14X-263 and 12X-03020), from US PHS (grant no. 5 R01 NSO7838), and from Föreningen Margaretahemmet, Turun Yliopistosäätiö, and Emil Aaltonen säätiö
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Söderfeldt, B., Kalimo, H., Olsson, Y. et al. Pathogenesis of brain lesions caused by experimental epilepsy. Acta Neuropathol 54, 219–231 (1981). https://doi.org/10.1007/BF00687745
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DOI: https://doi.org/10.1007/BF00687745