Abstracts

RATIONALE: The relationship of prolonged febrile seizures (FS) in the human to subsequent temporal lobe epilepsy is not fully understood. In the immature rat model, prolonged hyperthermia-induced seizures lead to long-term increased susceptibility of hippocampal circuits to excitatory input (Dube et al, Ann Neurol, 2000). However, the neuroanatomical changes involved in the mechanisms of this seizure-prone state remain unresolved. Aberrant growth of granule cell (GC) axons (mossy fibers) has been shown to drastically alter hippocampal circuits in several experimental epilepsy paradigms. Here we questioned whether prolonged FS in the immature rat can induce dentate gyrus (DG) mossy fiber sprouting, with consequent synaptic re-arrangements that may alter hippocampal excitability. METHODS: Immature Sprague Dawley rats (P10) subjected to hyperthermic seizures were compared with hyperthermic and normothermic controls. Timm-stained coronal and horizontal sections from animals surviving 3-5 months were analyzed without knowledge of treatment. Timm-labeled fibers traversing the GC layer (GCL) and encroaching on the inner molecular layer (IML) were counted, avoiding the tip and crest regions of the DG blades. RESULTS: Hyperthermic seizures increased aberrant mossy fiber growth (sprouting) substantially, as reflected by a significant (30-40%) increase in the number of Timm-stained fibers in GCL and IML, as well as by the increase in their diameter and length. CONCLUSIONS: Unlike the majority of early-life seizures, prolonged FS in the rat model result in mossy fiber sprouting. The mechanisms and precise consequences of this abnormal growth pattern require further studies. Supported by NS35439.