Effect of severe neonatal seizures on prepulse inhibition and hippocampal volume of rats tested in early adulthood

• Deficits in PPI have been observed in patients with schizophrenia.
• Structural changes in the hippocampus have been implicated in schizophrenia.
• Rats pups subjected to seizures presented deficits in PPI when tested in adulthood.
• Hippocampal volume was reduced in rats that experienced severe neonatal seizures.
• These results suggest that early seizures may raise risk for later schizophrenia.

Several lines of evidence indicate that the risk of developing schizophrenia is significantly enhanced following postnatal exposure to environmental insults occurring during the critical periods of early central nervous system development. The hippocampus is a brain structure that has been associated with the neuropathology of schizophrenia. Neonatal epileptic seizures in rat pups can affect the construction of hippocampal networks. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The aim of the present study was to investigate if prolonged epileptic seizures, occurring during postnatal brain development, alter prepulse inhibition (PPI) response of acoustic startle reflex and hippocampal volume of rats tested later in life (post-pubertal phase). Pilocarpine-induced status epilepticus (SE) was induced in postnatal days (PNDs) 7–9 in rat pups. On PND56, the animals were tested in the acoustic startle/PPI paradigm. Hippocampal volume was measured in histological brain slices using the Cavalieri's principle. Dorsal and ventral hippocampi were measured bilaterally. Our results demonstrate that animals subjected to SE presented deficits in PPI when tested in adulthood. Dorsal hippocampal volume was reduced in rats that experienced severe neonatal seizures.