Are morphologic and functional consequences of status epilepticus in infant rats progressive?

The present study examined whether status epilepticus (SE) induced by LiCl-pilocarpine in immature rats (postnatal day [P]12) interferes with normal development; leads to progressive epileptogenesis, or cognitive decline and to pathology similar to that seen in human temporal lobe epilepsy. We correlated the extent of pathologic changes with the severity of functional alterations or epilepsy. SE-induced changes were compared with those of rats with SE induced at P25. Animals of both ages were exposed to a battery of behavioral tests for up to 3 months after SE. Rats with SE at P12 showed mild retardation of psychomotor development and delayed habituation, whereas rats with SE at P25 showed no habituation. Assessment in adulthood using the Morris water maze test revealed that SE at both P12 and P25 led to cognitive impairment and that the severity of the impairment increased with age. A handling test revealed increased aggression in rats with SE at P25, but not in rats with SE at P12. Epilepsy was diagnosed with continuous video-electroencephalographic (EEG) monitoring for up to 7 d. P25 rats were monitored at 5 months after SE and seizures were detected in 83.3% of animals. P12 animals were divided into two groups and monitored at 5 or 7 months after SE. Both the severity and incidence of spontaneous recurrent seizures tended to progress with time, and their incidence increased from 50% to 87.5% at 5 and 7 months, respectively. Morphometric analysis and stereologic assessment of hilar neurons performed after video-EEG monitoring revealed atrophy of temporal brain structures, enlargement of lateral ventricles, and loss of hilar neurons in both age groups. In P12 rats, morphologic damage also tended to progress over time. Performance of animals in the Morris water maze correlated with the severity of damage, but not with seizure parameters.

► Risk of epilepsy increases with interval after early-life status epilepticus. ► Age at status epilepticus is decisive for semiology of spontaneous seizures. ► Status epilepticus-induced epilepsy and brain atrophy progressed in time. ► Extent of hippocampal damage was not associated with severity of epilepsy. ► Performance in Morris water maze did not correlate with severity of epilepsy.