Status epilepticus: the reversibility of calcium loading and acute neuronal pathological changes in the rat...

Light and electron microscopy (with the combined oxalate-pyroantimonate technique for the electron microscopic visualization of intracellular calcium) were used to compare the hippocampal pathology in rats killed immediately after 1.5-2 h of L-allylglycine-induced seizures with that in rats allowed 15-60 min of a seizure-free "recovery" period before perfusion fixation. Following 1.5 h of seizure activity, cellular pathology included astrocytic swelling and dark cell degeneration of pyramidal and polymorphic neurons. This was accompanied by a marked increase in the amount of calcium pyroantimonate deposits, particularly in swollen and disrupted mitochondria of CA1 and CA3 basal dendrites and in certain neuronal cell bodies in the CA1 and CA3 regions and the hilus. After a seizure-free period of between 30 and 60 min the hippocampi showed almost complete recovery except for a few remaining dark, shrunken cells. The majority of these were presumed to be interneurons. The ultrastructural changes were consistent with the observations by light microscopy. By 60 min, excess calcium deposits had disappeared except in the dark cells in which intracellular vacuoles retained deposits. We conclude that most of the pathological changes observed after 1.5 h of L-allylglycine induced status epilepticus, including the mitochondrial calcium "overload" are reversible. At 1 h after termination of status epilepticus apparently irreversible pathology (dark cell change, "ischaemic cell change") concerns predominantly the polymorphic neurons.