title: L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats.
abstract: OBJECTIVE
  This study investigated whether anticerebral ischemia new drug, l-3-n-butylphthalide (l-NBP), improved behavioral recovery and enhanced hippocampal neurogenesis after cerebral ischemia in rats.
  
  
  RESULTS
  The middle cerebral artery of rats was blocked for 2 h. The daily oral administrations of 30 mg/kg l-NBP or vehicle were begun from the second day until the rats were sacrificed. L-NBP treatment markedly increased 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the hippocampal dentate gyrus (DG) of injured hemisphere on day 28 after ischemia. The amount of newborn cells and newly mature neurons was also increased. The expressions of growth-associated protein-43 and synaptophysin were significantly elevated in l-NBP-treated rats. However, l-NBP markedly reduced the percentage of BrdU(+) /GFAP(+) cells. Additionally, the levels of catalytical subunit of protein kinase A (PKA), protein kinase B (Akt), and cAMP response element-binding protein (CREB) were significantly increased, and the activation of the signal transducer and activation of transcription 3 (STAT3) and the expressions of cleaved caspase-3 and Bax were obviously inhibited by l-NBP. Consequently, l-NBP attenuated the behavioral dysfunction.
  
  
  CONCLUSIONS
  It first demonstrates that l-NBP may improve the behavioral outcome of cerebral ischemia by promoting neurogenesis and neuroplasticity. Activation of CREB and Akt and inhibition of STAT3 signaling might be involved in.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xian-Fang
authors.initials: XF
authors.lastname: Rong
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D001572:Benzofurans; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C027125:3-n-butylphthalide; D051057:Proto-Oncogene Proteins c-akt
keywords: CREB; Cerebral ischemia; L-3-n-butylphthalide; Neurogenesis; Neuroplasticity