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| Content Provider | Springer Nature Link |
|---|---|
| Author | Huang, Chin Wei Wu, Sheng Nan Cheng, Juei Tang Tsai, Jing Jane Huang, Chao Ching |
| Copyright Year | 2009 |
| 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. |
| Starting Page | 305 |
| Ending Page | 316 |
| Page Count | 12 |
| File Format | |
| ISSN | 10298428 |
| Journal | Neurotoxicity Research |
| Volume Number | 17 |
| Issue Number | 4 |
| e-ISSN | 14763524 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2009-09-01 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Diazoxide Status epilepticus Diabetes ATP-sensitive potassium channel Neurobiology Pharmacology/Toxicology Neurochemistry Neurology Pharmaceutical Sciences/Technology Neurosciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Toxicology |
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