Diazoxide reduces status epilepticus neuron damage in diabetes.

Chin Wei Huang, Sheng Nan Wu, Juei Tang Cheng, Jing Jane Tsai, Chao Ching Huang

研究成果: 雜誌貢獻文章

17 引文 斯高帕斯(Scopus)

摘要

Diabetic hyperglycemia is associated with seizure severity and may aggravate brain damage after status epilepticus. Our earlier studies suggest the involvement of ATP-sensitive potassium channels (K(ATP)) in glucose-related neuroexcitability. We aimed to determine whether K(ATP) agonist protects against status epilepticus-induced brain damage. Adult male Sprague-Dawley rats were divided into two groups: the streptozotocin (STZ)-induced diabetes (STZ) group and the normal saline (NS) group. Both groups were treated with either diazoxide (15 mg/kg, i.v.) (STZ + DZX, NS + DZX) or vehicle (STZ + V, NS + V) before lithium-pilocarpine-induced status epilepticus. We evaluated seizure susceptibility, severity, and mortality. The rats underwent Morris water-maze tests and hippocampal histopathology analyses 24 h post-status epilepticus. A multi-electrode recording system was used to study field excitatory postsynaptic synaptic potentials (fEPSP). RNA interference (RNAi) to knockdown Kir 6.2 in a hippocampal cell line was used to evaluate the effect of diazoxide in the presence of high concentration of ATP. Seizures were less severe (P <0.01), post-status epilepticus learning and memory were better (P <0.05), and neuron loss in the hippocampal CA3 area was lower (P <0.05) in the STZ + DZX than the STZ + V group. In contrast, seizure severity, post-status epilepticus learning and memory, and hippocampal CA3 neuron loss were comparable in the NS + DZX and NS + V groups. fEPSP was lower in the STZ + DZX but not in the NS + DZX group. The RNAi study confirmed that diazoxide, with its K(ATP)-opening effects, could counteract the K(ATP)-closing effect by high dose ATP. We conclude that, by opening K(ATP), diazoxide protects against status epilepticus-induced neuron damage during diabetic hyperglycemia.

原文英語
頁(從 - 到)305-316
頁數12
期刊Neurotoxicity Research
17
發行號4
DOIs
出版狀態已發佈 - 五月 2010
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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