Abstracts

Lithium pilocarpine status epilepticus (LiPC) that is allowed to continue uninterrupted results in widespread neuronal injury in the developing rat brain. The hippocampus of the rat shows a developmental pattern of SE-induced injury that is age specific. Using pharmacological interventions to stop SE reduces the extent of the hippocampal injury. Here, we try to determine whether there exits a temporal window to stop SE before the onset of widespread injury. Under isoflurane anesthesia, 2 and 3-wk old Wistar rat pups were implanted with wireless recording modules (Data Sciences Inc.). The recording leads were placed onto the dura and secured with adhesive. Rats were pretreated 16-20hr with 3mEq LiCl (ip), followed by 60mg/kg PC (sc) to induce SE at postnatal day 14 or 21. Control rats were treated identically, but given saline in place of PC. 30, 90, 120, 150 or 180 min after the initiation of SE or saline injection, rats were given 5mg/kg diazepam + 25mg/kg phenobarbital (ip). EEGs were analyzed offline for initiation and cessation of SE using Harmonie seizure detection software (Stellate Sytems). Rats were killed 24hr after the start of SE, and their brains cut at 8microns for cell counts using H[amp]E as a marker of neuronal injury. The onset of SE was faster in the younger age group (8.2 [plusmn]1.8 min vs. 21.6 [plusmn] 5.3min p[lt]0.07) as was the time to stop status SE at 30min (13.4 [plusmn] 4.1min vs. 35.3 [plusmn] 12.0min p[lt]0.07) or 90min of seizures (9.8 [plusmn] 3.6min vs. 64.4 [plusmn] 7.2min p[lt] 0.05). There were no significant differences in the time to stop SE after 120 or 150 min in the P14 animals as compared to the shorter durations. Histological examination of neuronal injury after 24 hrs revealed that extrahippocampal injury preceded extensive neuronal injury to the hippocampus after SE at both ages, but there was a non-statistically significant increase in the number of damage dentate granule and CA1 neurons in the P14 rats. Increasing the duration of SE from 30 to 90min exacerbated hippocampal neuronal injury only in the hilus of the P21 age group. While high doses of diazepam (30mg/kg) were found to damage neurons in P14 rat pups, the dose used in this study (5mg/kg) did not result in detectible injury in control animals. While the younger age group in our study showed an increased susceptibility for the onset of SE, their subsequent responsiveness to treatment after varying durations of SE suggests a larger therapeutic window for intervention as compared to animals just one week older. Additionally, our data suggest neuroprotective strategies in the immature brain should consider patterns of injury that are age specific in response to SE. (Supported by NS046516 [amp] the DAPA Foundation (RS), AEAC association (SA).)