Hippocampal sclerosis is a common pathological finding in patients with
temporal lobe epilepsy, including children, but a causal relationship to early-life
seizures remains in question. Neonatal
status epilepticus in animals can result in neuronal death within the hippocampus, although macroscopic features of hippocampal shrinkage are not evident at adulthood. Here, we examined electrophysiological and pathological consequences of focally evoked
status epilepticus triggered by intra-amygdala microinjection of
kainic acid in postnatal day 10 rat pups. Neonatal
status epilepticus resulted in extensive neuronal death in the ipsilateral hippocampal CA1 and CA3 subfields and hilus, as assessed by DNA fragmentation and
Fluoro-Jade B staining 72 hours later. The contralateral hippocampus was not significantly damaged. Histopathology at P55/P65 revealed unilateral
hippocampal sclerosis (grade IV, modified Wyler/Watson scale) comprising >50% CA1 and CA3 neuron loss and
astrogliosis. Additional features included
hydrocephalus ex vacuo, modest dentate granule cell layer widening, and altered
neuropeptide Y immunoreactivity indicative of synaptic rearrangement. Hippocampal
atrophy was also evident on magnetic resonance imaging. Depth
electrode recordings at adulthood detected spontaneous
seizures that involved the ipsilateral hippocampus and amygdala. A significant positive correlation was found between hippocampal pathology grade and both frequency and duration of epileptic
seizures at adulthood. The current study demonstrates that experimental neonatal
status epilepticus can result in classical unilateral
hippocampal sclerosis and
temporal lobe epilepsy.