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

15 引文 (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

Diazoxide
Status Epilepticus
Streptozocin
Medical problems
Neurons
Adenosine Triphosphate
Seizures
Synaptic Potentials
Excitatory Postsynaptic Potentials
RNA Interference
Hyperglycemia
Rats
Brain
Learning
RNA
Data storage equipment
KATP Channels
Pilocarpine
Experimental Diabetes Mellitus
Lithium

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

引用此文

Diazoxide reduces status epilepticus neuron damage in diabetes. / Huang, Chin Wei; Wu, Sheng Nan; Cheng, Juei Tang; Tsai, Jing Jane; Huang, Chao Ching.

於: Neurotoxicity Research, 卷 17, 編號 4, 05.2010, p. 305-316.

研究成果: 雜誌貢獻文章

Huang, Chin Wei ; Wu, Sheng Nan ; Cheng, Juei Tang ; Tsai, Jing Jane ; Huang, Chao Ching. / Diazoxide reduces status epilepticus neuron damage in diabetes. 於: Neurotoxicity Research. 2010 ; 卷 17, 編號 4. 頁 305-316.
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abstract = "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.",
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