Pilocarpine-induced status epilepticus causes acute interneuron loss and hyper-excitatory propagation in rat insular cortex

Abstract

Recent clinical studies have shown that the insular cortex (IC) is involved in temporal lobe epilepsy and suggested that the IC mediates spreading of epileptic activity from the temporal lobe, including the hippocampus and amygdala, to the frontal cortex. However, little is known about anatomical and physiological features of the IC in models of temporal lobe epilepsy. The present study evaluated the distribution pattern of GABAergic interneurons, especially parvalbumin (PV)- and somatostatin (SS)-immunopositive neurons, and excitatory propagation pattern in the IC of rats 4-7 days and 2 months after pilocarpine-induced status epilepticus (4-7 d and 2 m post-SE rats, respectively). The number of PV-immunopositive neuron profiles in the agranular IC (AI) significantly decreased by 24.6% and 41.5% in 7 d and 2 m post-SE rats, respectively. The dysgranular and granular IC (DI+GI) exhibited only 5.2% loss of PV-immunopositive neurons in 7 d post-SE rats, while 2 m post-SE rats showed 30.4% loss of PV-immunopositive neurons. There was no significant change of the SS-immunopositive neuron profile numbers in the AI and DI+GI of 7 d and 2 m post-SE rats. The regions with decreased numbers of PV-immunopositive neuron profiles overlapped with those where many degenerating cells were detected by Fluoro-Jade B staining. The area of excitatory propagation responding to electrical stimulation of the caudal AI was expanded in 4-7 d post-SE rats, and excitation frequently propagated to the frontal cortex including the motor cortex. Optical signals in the AI of 4-7 d post-SE rats were larger in amplitude than those of controls. In contrast to the AI, the DI of 4-7 d post-SE rats showed similar excitatory propagation pattern and amplitude to that of controls. These results suggest that the region-specific loss of PV-immunopositive neurons occurred in the AI 4-7 d after pilocarpine-induced status epilepticus, which may play an important role in facilitating excitatory propagation in the IC.