Abstracts

Rationale: Status epilepticus (SE) is most frequent at the extremes of life; yet, many prior pathophysiological studies of SE were performed in adult animals. As the pathophysiological process underlying SE in the immature brain may differ from that in the mature brain, we have characterized SE in the immature brain using electrographic, immunohistochemical, and patch clamp electrophysiological techniques. Methods: SE was induced in postnatal day 10-12 Sprague Dawley rats via the subcutaneous injection of kainic acid (KA) 3 mg/kg. Electrographic recordings were obtained from monopolar electrodes placed in the right and left hippocampi, left frontal cortex, and right parietal cortex. Standard immunohistochemical techniques were used to characterize Fos-like immunoreactivity (Fos-LI), an indirect measure of neuronal depolarization and activity, in the hippocampus in brain slices from SE-treated animals obtained 2 and 4 hours after KA injection and from saline-injected controls. GABA_A receptor (GABAR)-mediated synaptic currents (sIPSCs) were recorded using standard whole cell patch clamp techniques from CA1 pyramidal neurons (PNs) and dentate granule cells (DGCs) in hippocampal slices from SE-treated animals (SE-treated slices) and from naïve controls. Results: Following injection of KA, recurrent behavioral and electrographic seizures were observed. Behavioral changes progressed through a regular sequence of hindpaw scratching, the loss of postural control and turning on the side with clonic or tonic-clonic movements, and the late onset of wet dog shakes. Electrographically, ictal bursts occurred no sooner than 30 minutes after KA injection and were 1-3 minutes in duration. Although the interictal period between bursts decreased during the 4 hours of EEG recording, continuous ictal bursts ≥ 5 minutes did not occur. At 2 and 4 hours after KA injection, induction of Fos-LI was observed in the cornus Ammons (CA1 and CA3) but not in the dentate gyrus (DG). As regional heterogeneity in FOS-LI suggests prolonged neuronal depolarization in the CA but not in the DG, we hypothesized that GABAR-mediated synaptic transmission in the CA but not the DG would be altered. Compared to controls, sIPSCs recorded from PNs in SE-treated slices were distinct. At 2 hours after KA injection, amplitude was reduced; and at 4 hours after KA injection, there was a reduction in both amplitude and frequency. In contrast, the amplitude and frequency of sIPSCs recorded from DGCs in SE-treated slices obtained 2 hours after KA injection were similar to controls. Conclusions: In the immature brain, SE was characterized by recurrent seizures resulting in neuronal activation and altered GABAR-mediated synaptic inhibition in the CA. This finding is in contrast to the prolonged seizures of SE in the mature brain that result in reduced GABAergic inhibition in both the CA and DG. Additional studies are required to further characterize the differences in SE in the immature and mature brain.