BACKGROUND:Mitochondrial damage plays a key role in neuronal damage. OBJECTIVE:To observe ultrastructural damage to mitochondria and nuclei,as well as caspase-3 expression,in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats. DESIGN,TIME AND SETTING:The neuropathological,randomized,controlled study was performed at the Animal Experimental Center,Shandong University,China in May 2008. MATERIALS:A total of 75 healthy,adult,male,Wistar rats were randomly assigned into model (n = 45) and control(n = 30) groups.Lithium-pilocarpine(Sigma,USA) was used in this study. METHODS:Rats in the model group were intraperitoneally injected with lithium chloride(3 mEq/kg), and 24 hours later with pilocarpine(45 mg/kg),to induce seizures for 2 hours.Rats in the control group were intraperitoneally infused with the same volume of saline.Rat hippocampal CA3 tissue was obtained at 3,12,and 24 hours following status epilepticus. MAIN OUTCOME MEASURES:Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope. caspase-3 mRNA levels were quantified by semiquantitative RT-PCR. RESULTS:After 3 hours of status epilepticus,mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy.Nuclei with marginated chromatin were observed after 24 hours status epilepticus.RT-PCR results demonstrated increased caspase-3 expression at 12 hours,and significantly increased expression at 24 hours following termination of status epilepticus.This was in accordance with acidophilia occurrence,as indicated by hematoxylin-eosin staining,and time of ultrastructural damage to nuclei. CONCLUSION:In lithium-pilocarpine-induced status epilepticus rat models,ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages,followed by increased caspase-3 expression and nuclear changes.These results suggested that mitochondrial damage plays a key role in neuronal damage following status epilepticus. BACKGROUND: Mitochondrial damage plays a key role in neuronal damage. OBJECTIVE: To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats. : The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008. MATERIALS: A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model (n = 45) and control METHODS: Rats in the model group were intraperitoneally injected with lithium chloride (3 mEq / kg), and 24 hours later with pilocarpine (45 mg (n = 30) groups. Lithium-pilocarpine / kg), to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was at 3,12, and 24 hours following status epilepticus. MAIN OUTCOME MEASURES: Neuronal changes were observe Results: After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results in increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence , as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei. CONCLUSION: In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes.These results suggest that mitochondrial damage plays akey role in neuronal damage following status epilepticus.