Chronic Cellular Hyperexcitability in Elderly Epileptic Rats with Spontaneous Seizures Induced by Kainic Acid Status...

Emerging data indicate that age-related brain changes alter seizure susceptibility, seizure-associated neurodegeneration, and responsiveness to AEDs. The present study assessed long-term animal survival in the Kainic Acid (KA) model along with in-vivo spontaneous seizure frequency, cellular hyperexcitability in CA1 in-vitro and in-vivo in subiculum, and responsiveness of in-vitro CA1 hyperexcitability to topiramate. Sprague-Dawley male rats were given KA to induce convulsive status epilepticus (KA-SE) at 2-3 months of age. The one-month mortality after KA-SE was 27%. One-month survivor rats had 37% sudden unexplained late mortality after KA-SE as compared to none in saline controls during their second year of life. In-vivo seizure frequency was examined prior to terminal experiments. The diurnal average seizure frequency in the KA-SE group at age 2 years was 1.06 ± 0.24 seizures/hour while no seizures were observed in the saline age-matched controls (p<0.001). In-vitro recordings of CA1 pyramidal neurons revealed that depolarizing current injection from -60 mV evoked an increased number of action potentials in the aged KA-SE group compared to controls (p<0.002). Topiramate exhibited dose-dependent inhibition of action potential firing evoked by current injections into CA1 pyramidal neurons of KA-SE rats. In subiculum, KA-SE rats had frequent interictal spikes associated with high frequency oscillations while only rare spontaneous EPSPs were recorded in saline controls. Our experiments revealed that the hippocampal formation of aged epileptic rats shares features of hyperexcitability previously described in young adult epileptic rats using the KA model.