The kindling model of epilepsy
Morphologic rearrangements of kindled animals
Identification of neuronal rearrangements in the brain of kindled animals has provided a potential structural explanation for the hyperexcitability of the kindled brain. Sutula and colleagues were the first to demonstrate the sprouting and permanent reorganization of the mossy fiber axons of the dentate granule cells of the hippocampus of kindled animals (Sutula et al., 1988; Cavazos et al., 1991). They subsequently demonstrated a 40% loss of neurons in the dentate hilus of animals in which 30 kindled seizures had been evoked (Cavazos & Sutula, 1990). This latter observation is important for two reasons. It demonstrates that periodic seizures without overt cyanosis are sufficient to induce neuronal loss and at least part of the picture of Ammon's horn sclerosis; this, in turn, suggests that recurrent isolated complex partial seizures, not merely status epilepticus, may be sufficient to kill neurons in humans. It also suggests that part of the mechanism of the mossy fiber sprouting involves a denervation or loss of synaptic input into the inner third of the granule cell dendrites.
The functional consequences of the mossy fiber rearrangements in the kindled brain and in other models remain controversial. Whether the net effect of the synaptic rearrangements is an elevated or reduced seizure threshold has generated intense arguments.