Temporal lobe epilepsy is a common form of epilepsy in human adults, associated with a unique pattern of damage referred to as Ammon's horn Sclersis (AHS). It has been suggested that this type of damage is the result of seizures early in life. AHS is characterized by cell loss of the CA3 and CA4 areas and sprouting of mossy fibre terminals in the supragranular layer of the hippocampal fascia dentate. Experimental evidence indicates that in adult rats, a similar pattern of hippocampal change occurs following seizures induced by kainic acid or kindling. Preliminary studies in adult rats indicate that seizure induced hippocampal damage can further be characterized by the presence of acute neuronal degeneration, proliferation of astrocytes, changes in synaptic excitation/ inhibition and GABA-A gene expression. In contrast, preliminary studies in rats younger than 15 days indicate that there appears to be an absence of seizure induced changes in the hippocampus following kainic acid seizures and kindling despite these seizures are more severe than in adults. It is hypothesized that 1) seizure induced hippocampal changes are age- dependent 2) the presence of damage, regardless of whether the damage results from seizures or an unrelated injury, corresponds with an increase in subsequent seizure susceptibility and finally 3) once the brain is injured, damage will be assessed both acutely and chronically by a variety of neuroanatomic, neurophysiologic and molecular techniques. Alterations in seizure susceptibility will be studied in rats that had seizures or lesions at a young age. The results of these studies are clinically relevant, particularly in children. They may help establish when seizures are likely and not likely to produce hippocampal damage, so that appropriate treatment strategies can be applied.
