BACKGROUND: Apoptosis and necrosis are cellular death mechanisms that are induced in glioma cells following gamma knife irradiation. Increased apoptosis is essential for maintaining and enhancing treatment efficacy.OBJECTIVE: To observe apoptotic and necrotic mechanisms of rat glioma models induced by gamma knife treatment and to analyze the influences of irradiation doses on apoptosis and necrosis. DESIGN: Controlled animal experiment. SETTING: Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital.MATERIALS: Eighteen female specific pathogen free Sprague Dawley rats, weighing 180-210 g and 5-6 weeks old, were purchased from the Experimental Animal Center, Medical College of Suzhou University. Rat C6 glioma cells were purchased from the cell bank of Chinese Academy of Sciences. Annexin V-FITC Reagent Kit (Bender Med System. Company, USA) and a flow cytometer (Becton Dickinson FACSCalibur) were provided.METHODS: The experiment was conducted at the Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital from December 2006 to May 2007. All rats were inoculated with C6 glioma cells, i.e., 4 μL of a C6 glioma cell suspension was injected 5 mm deep in the cortex. All rats were divided randomly into a model group, 9-Gy treatment group, and 12-Gy treatment group. There were six rats in each group.MAIN OUTCOME MEASURES: Apoptosis and necrosis of normal brain tissue and glioma were observed by Flow Cytometry one week after irradiation, and pathological changes to tumor tissue were identified by HE staining.RESULTS: Eighteen rats were initially selected for the study: two rats from the model and 12-Gy treatment groups died from accidental anesthesia. The remaining 16 rats were included in the final result analysis. Cellular apoptosis and necrosis: apoptosis and necrosis were significantly increased in the treatment groups after gamma knife irradiation, compared to the model group (P < 0.05). Apoptosis was greater in the 9-Gy treatment group compared to the 12-Gy treatment group (P < 0.01). Necrosis was significantly reduced in the 9-Gy treatment group compared to the 12-Gy treatment group (P < 0.01). Pathological changes: The necrosis of the center of tumor tissue appeared in the 9, 12 Gy treatment group. Cells dispersed in the necrosis region and the density of cells was higher with the longer distance from the necrosis region. There were patches of pycnotic cells with different period between the edge and center of the necrosis region,and the cellular dropsy could be seen. Moreover, the amount of necrosis was greater with increasing doses of irradiation.CONCLUSION: Apoptosis and necrosis are cellular death mechanisms induced by gamma knife treatment of gliomas. Cellular necrosis increased with greater irradiation doses.