Association between the density of mossy fiber sprouting and seizure frequency in experimental and human temporal lobe epilepsy

Purpose: If the sprouting of granule cell axons or mossy fibers in the dent ate gyrus is critical for the generation of spontaneous seizures in tempora l lobe epilepsy (TLE), one could hypothesize that epileptic animals or huma ns with increased sprouting would have more frequent seizures. This hypothe sis was tested by analyzing the data gathered from experimental and human e pilepsy. Methods: In experiment I(rats with "newly diagnosed" TLE), self-sustained s tatus epilepticus was induced in rats by electrically stimulating the amygd ala. Thereafter, the appearance of spontaneous seizures was monitored by co ntinuous video-electroencephalography (EEG) until the animal developed two spontaneous seizures and for 11 d thereafter. Rats were perfused for histol ogy, and mossy fibers were stained using the Timm method. In experiment II (rats with "recently diagnosed" TLE), status epilepticus was induced in rat s and the development of seizures was monitored by video-EEG for 24 Nd ever y other day for 60 days. All animals were then perfused for histology. In e xperiment III (rats with "chronic" TLE), animals were monitored by video-EE G for 24 Nd every other day for 6 months before histologic analysis. To ass ess mossy fiber sprouting in human TLE, hippocampal sections from 31 patien ts who had undergone surgery for drug-refractory TLE were stained with an a ntibody raised against dynorphin. Results and Conclusions: Our data indicate that the density of mossy fiber sprouting is not associated with the total number of lifetime seizures or t he seizure frequency in experimental or human TLE.