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AIM To investigate the effects of ganoderma lucidum spores on caspase 8 and nestin in brain tissue of rats with epilepsy induced by pentylenetetrazol (PTZ), and to further study the pathogenesis of epilepsy and the anti-epilepsy mechanism of ganoderma lucidum spores.METHODS Thirty-six male Sprague-Dawley rats were divided into control, PTZ epilepsy and ganoderma lucidum spores (GLS) groups.RESULTS The results showed that caspase 8-positive cell in rats of PIZ model group were higher than normal control and GLS group, while the content of caspase 8-positive cell were decreased in the GLS group compared with the epileptic model group.The content of nestin were higher in PTZ model group than those of control group and GLS group at in cortex and hippocampus,also The content of nestin in GLS group were higher than control group.CONCLUSION Ganoderma lucidum spores can effectively reduce the expression of apoptosis cell and inhibit the caspase 8 activations in the epileptic rats brain tissue, strengthen the function of anti-oxidize in brain tissue, and can supply recovering of epilepsy nerve cell with important basis by reducing the content of nestin neural internality protect mechanism can be strengthened to reduce the damage on nerve system induced by falling sickness.Ganoderma lucidum spores is an assistant medicine to cure epilepsy, it can be very useful in clinic application.