title: 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.
authors.affiliation: Department of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang 150081, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150086, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150086, China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang 150081, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Chi
authors.affiliation: Department of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang 150081, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150086, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, Heilongjiang 150086, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Cancer Hospital Affiliated to Harbin Medical University, 150 Haping Road, Harbin, Heilongjiang 150081, China. Electronic address: wangguonian2015@126.com.
authors.forename: Guonian
authors.initials: G
authors.lastname: Wang
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D007211:Indoles / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D007211:Indoles; D008301:Maleimides; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D006862:Hydrogen Sulfide
keywords: Aquaporin 4; Brain edema; Hydrogen sulfide; Middle cerebral artery occlusion; Protein kinase C