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Hydrogen sulfide induces neuroprotection against experimental stroke in rats by down-regulation of AQP4 via activating PKC.

Abstract
Hydrogen sulfide (H2S) is now known as an important neuromodulator in the central nervous system. The aim of the current study was to investigate whether exogenous H2S gas can attenuate brain edema induced by experimental stroke and to clarify the potential mechanisms. Rats underwent 2-h middle cerebral artery occlusion (MCAO) and received 40 ppm or 80 ppm H2S inhalation for 3h at the beginning of reperfusion. The effects of H2S were investigated by evaluating neurological function, infarct size, brain edema volume, and aquaporin4 (AQP4) protein expression at 24h after reperfusion. Moreover, to explore the possible mechanisms for the neuroprotective effects of H2S, protein kinase C (PKC) activity was detected and a PKC inhibitor, Go6983, was used via intracerebral ventricular injection. Our results showed that 40 ppm or 80 ppm H2S inhalation significantly reduced neurological deficits, infarct size, and brain edema after MCAO. The expression of AQP4 in the peri-infarct area of brain was also inhibited after inhalation of H2S. PKC was activated by H2S treatment and the PKC inhibitor attenuated the neuroprotection of H2S with an increased AQP4 expression at the same time. In conclusion, H2S inhalation attenuates brain edema, reduces infarct volume, and improves neurologic function in a rat experimental stroke model. The therapeutic benefits of H2S inhalation are associated with down-regulation of AQP4 expression via activating PKC.
AuthorsXia Wei, Bing Zhang, Long Cheng, Meng Chi, Lin Deng, Hong Pan, Xuan Yao, Guonian Wang
JournalBrain research (Brain Res) Vol. 1622 Pg. 292-9 (Oct 05 2015) ISSN: 1872-6240 [Electronic] Netherlands
PMID26168888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • 2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
  • Aqp4 protein, rat
  • Aquaporin 4
  • Indoles
  • Maleimides
  • Neuroprotective Agents
  • Protein Kinase Inhibitors
  • Protein Kinase C
  • Hydrogen Sulfide
Topics
  • Administration, Inhalation
  • Animals
  • Aquaporin 4 (metabolism)
  • Brain (drug effects, pathology, physiopathology)
  • Brain Edema (drug therapy, pathology, physiopathology)
  • Disease Models, Animal
  • Down-Regulation (drug effects)
  • Hydrogen Sulfide (administration & dosage)
  • Indoles (pharmacology)
  • Infarction, Middle Cerebral Artery
  • Male
  • Maleimides (pharmacology)
  • Neuroprotective Agents (administration & dosage)
  • Protein Kinase C (antagonists & inhibitors, metabolism)
  • Protein Kinase Inhibitors (pharmacology)
  • Random Allocation
  • Rats, Sprague-Dawley
  • Stroke (drug therapy, pathology, physiopathology)

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