Objective    To investigate the relation between the pathogenesis of epilepsy and the mossy fiber sprouting (MFS) by using gamma knife (GK) radiation in rat model.     Methods    Seventy-four Wistar rats were randomly divided into 3 experimental groups: control group (normal rats

group A); rats that underwent kainic acidinduction alone (KA rats

group B); KA rats treated by 40 Gy gamma knife (group C). Conventional histopathological method and electron microscope were used to observe morphological changes in hippocampal formation. In addition

Timm’s silver sulfide staining was used to examine the effect of  GK on MFS.     Results    Hippocampal neuronal degeneration and necrosis

especially in CA1 and CA3 and inner molecular layer (IML) of the dentate gyrus were seen in group B. Fewer apoptotic neurons and milder lesions in neurons at the corresponding time point were revealed in group C than group B. Timm’s staining showed that multiple aberrant Timm’s granules were found in the IML of the dentate gyrus in groups B and C

but not in group A

The transparent layer of CA3 section of the hippocampus was more pronounced in groups B and C than A（P0.001）. No significant difference was noted regarding MFS between group B and group C during 1-14 days（P0.05）; 28-42 days later

it became significantly different（P0.05）.     Conclusion    Changes of cell modality--mossy fiber sprouting of hippocampus may play an important role in the pathogenesis of epilepsy. Gamma knife (40 Gy) has definitive effect on inhibiting neuron damage

in which inhibiting MFS in the hippocampus is main mechanism to eliminate epilepsy.