title: Neuroprotective effects of artemisinin against isoflurane-induced cognitive impairments and neuronal cell death involve JNK/ERK1/2 signalling and improved hippocampal histone acetylation in neonatal rats.
abstract: OBJECTIVE
  This study was performed to assess the effect of artemisinin against isoflurane-induced neuronal apoptosis and cognitive impairment in neonatal rats.
  
  
  METHODS
  Artemisinin (50, 100 or 200 mg/kg b.wt/day; oral gavage) was administered to separate groups of neonatal rats starting from postnatal day 3 (P3) to postnatal day 21 (P21). On postnatal day 7 (P7), animals were exposed to inhalation anaesthetic isoflurane (0.75%) for 6 h.
  
  
  RESULTS
  Neuronal apoptosis following anaesthetic exposure was significantly reduced by artemisinin. Isoflurane-induced upregulated cleaved caspase-3, Bax and Bad expression were downregulated. Western blotting analysis revealed that treatment with artemisinin significantly enhanced the expression of anti-apoptotic proteins (Bcl-2, Bcl-xL, c-IAP-1, c-IAP-2, xIAP and survivin). Artemisinin increased the acetylation of H3K9 and H4K12 while reducing the expression of histone deacetlyases (HDACs) - HDAC-2 and HDAC-3. Isoflurane-induced activation of JNK signalling and downregulated ERK1/2 expression was effectively modulated by artemisinin. General behaviour of the animals in open-field and T-maze test were improved. Morris water maze test and object recognition test revealed better learning, working memory and also better memory retention on artemisinin treatment.
  
  
  CONCLUSIONS
  Artemisinin effectively inhibited neuronal apoptosis and improved cognition and memory via regulating histone acetylation and JNK/ERK1/2 signalling.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Ping-le
authors.initials: PL
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Hai-Ming
authors.initials: HM
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Han
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037621:Artemisinins; D006657:Histones; D018696:Neuroprotective Agents; C031327:artemisinin; D007530:Isoflurane
keywords: artemisinin; histone acetylation; isoflurane; mitogen-activated protein kinases; neuroapoptosis