Abstracts

RATIONALE: Temporal lobe epilepsy (TLE) is a partial epilepsy characterized by limbic-originated seizures (automatisms, stereotyped behavior) followed by secondarily generalized seizures. Several clinical and experimental data indicate that propagation of epileptic discharges to other structures can cause a secondary epileptogenesis process (kindling-like effects). In the present work, we explore the neuropathology and in vitro electrophysioly neocortex in a the pilocarpine model of TLE.
METHODS: Pilocarpine-treated epileptic animals showing 8-10 seizures and saline-injected control rats were selected for the neuropathological and immunocytochemical (ICC)studies. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and counterstained with cresyl violet, celestine blue and fuscin acid for the identification of different histological characteristics. Several antibodies were used for ICC such as anti-GABA transporter 1 (GAT-1), anti- Glutamic Acid Decarboxylase (GAD-65), anti-Neurofilament (SMI-311), anti-Parvalbumin (PV). In vitro electrophysiology (extracellular and intracellular recordings) was performed in coronal and sagital slices containing sensorimotor and somatosensory cortex. Field potentials were recorded from layer II-III after stimulation of layer VI/white matter border. Intrinsic properties and firing pattern were studied after intracellular recordings from neurons in layer II,III and V.
RESULTS: Nissl staining showed an evident decrease of cortical thickness in epileptic rats when compared with control rats. This alteration was particularly evident in superficial layers (II-IV), with a relative enlargement of layers V and VI. SMI-311 staining showed a decrease of cellular immunorreactivity, particularly in layers II and III, and an abnormal dendritic arborization of pyramidal neurons indicating a process of reorganization. PV-immunoreactivity showed a dramatic reduction of PV-positive cells and terminals as well as laminar disorganization in chronic epileptic rats. Some slices from epileptic animals exhibited pronounced hyperexcitability and deficit in paired-pulse inhibition. There were no significant differences in passive intrinsic properties of neocortical layer V cells between the control and epileptic animals. However, it was possible to observe a higher proportion of burst-generating neurons in different areas of chronic epileptic rats.
CONCLUSIONS: Taken together, our findings indicate that neocortical areas express chronic hyperexcitability as result of abnormal local network and intrinsic neuronal properties. Our findings indicate abnormal cytoarchitectural and electrophysiological properties of neocortex in TLE.
Support: PRONEX, FAPESP, CNPq, CAPES from Brazil.