Abstracts

The lithium-pilocarpine (Li-pilo) model reproduces the main characteristics of human mesial temporal lobe epilepsy. This model is characterized by an acute status epilepticus (SE) followed by a latent seizure free period and spontaneous recurrent seizures. Extensive damage and neuronal loss are present in hippocampus, thalamus, amygdala and ventral cortices. Synaptopysin is a protein expressed at presynaptic vesicles and is known as a neuronal marker of synaptogenesis. GAP-43 is a specific marker for axons and growth cones. It is expressed at high levels during nervous system development, and its dramatic synthesis was observed in injured and regenerating tissue. Here, we examined the features of neuronal reconstruction after SE using these neuronal markers. SE was induced by LiCl (3 meq/kg) 18 h before pilocarpine was injected (25 mg/kg) to adult male rats. Control rats received LiCl and saline instead of pilocarpine. Expression of synaptophysin and GAP-43 was examined at 7 days after SE. Sections were cut with a vibratome and free floating sections were stained with specific antibodies. Image analysis was performed using a CCD camera mounted onto a light microscope and connected to a computer. The optical density was measured by means of an image processing system. Immunoreactivity of synaptophysin was increased in piriform and entorhinal cortex of the Li-pilo group, compared to the control group, and that of GAP-43 decreased in the same regions. In medial and lateral thalamus and amygdala, GAP-43 immunoreactivity decreased in Li-pilo rats, while synaptophysin did not show any significant difference compared to control animals. In hippocampus, immunoreactivity of both synaptophysin and GAP-43 was similar in control and Li-pilo rats. The higher expression of synaptophysin and lower expression of GAP-43 in ventral cortices may relate to severe neuronal loss. The decrease of GAP-43 expression in thalamus and amygdala occurs in regions less damaged but undergoing early neuronal loss as the ventral cortices. The expression of synaptophysin and GAP-43 was not altered in CA1 in which neuronal loss is delayed compared to the former regions. A time-dependent study of the expression of these proteins has been undertaken in order to clarify these regional differences and the potential relationship between time-dependent neuronal loss and the expression of these proteins. (Supported by INSERM U405)