Neuronal injury and brain-derived neurotrophic factor expression in a rat model of amygdala kindling seizures Differences in brain regions and kindling courses

BACKGROUND:Studies have demonstrated that brain-derived neurotrophic factor(BDNF) has a dual effect on epilepsy.However,the relationship between epilepsy-induced brain injury and BDNF remains poorly understood.OBJECTIVE:According to ultrastructural and molecular parameters,to detect the degree of neuronal injury and BDNF expression changes at different brain regions and different kindling times to determine the effects of BDNF on epilepsy-induced brain injury.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment based on neuropathology and molecular biology was performed at the Department of Physiology and Department of Pathology,Basic Medical College of Jilin University in 2003.MATERIALS:UltraSensitive SP kit for immunohistochemistry(Fuzhou Maxim Biotechnology,China),BDNF antibody(concentrated type,Wuhan Boster Biological Technology,China),JEM-1000SX transmission electron microscopy(JEOL,Japan),and BH-2 light microscope(Olympus,Japan) were used in the present study.METHODS:Wistar rats were randomly assigned to control(n = 6),sham-surgery(n = 6),and model(n = 60) groups.The control group rats were not treated;an electrode was embedded into the amygdala in rats from the sham-surgery and model groups;an amygdala kindling epilepsy model was established in the model group.MAIN OUTCOME MEASURES:Pathological changes in the temporal lobe and hippocampus were observed by light and electron microscopy at 1,3,7,14,and 21 days following kindling,and BDNF expression in the various brain regions was determined by immunohistochemistry.RESULTS:In the model group,temporal lobe cortical and hippocampal neurons were swollen and the nuclei were laterally deviated.There were also some apoptotic neurons 3 days after kindling.The nucleoli disappeared and the nuclei appeared broken or lysed,as well as slight microglia hyperplasia,at 7 days.Electron microscopic observation displayed chromatin aggregation in the nuclei and slight mitochondrion swelling 3 days after kindling.Injury changes were aggravated at 7 days,characterized by broken cytoplasmic membrane and pyknosis.With the development of seizure,the number of BDNF-positive neurons in the hippocampus and temporal lobe increased and peaked at 7 days.Moreover,hippocampal and cortical temporal lobe injury continued.Following termination of electrical stimulation after 7 days of kindling,BDNF expression decreased,but continued to be expressed,up to 21 days of kindling.In addition,the number of temporal and hippocampal BDNF-positive neurons was greater than the control group.CONCLUSION:Brain injury and BDNF expression peaked at 7 days after kindling,and hippocampal changes were significant.