title: Huatuo Zaizao pill promotes functional recovery and neurogenesis after cerebral ischemia-reperfusion in rats.
abstract: BACKGROUND
  Ischemic stroke is the third leading cause of death in adults worldwide and is the first leading cause of long-term disability. Neurogenesis plays an important role in promoting behavioral recovery after stroke. Huatuo Zaizao pill (HT), a traditional Chinese medicine, has been used clinically in China to promote the rehabilitation after stroke, but the underlying mechanism of action was still unclear. This study is to investigate the effects of HT on the functional recovery in a rat model of cerebral ischemia-reperfusion (I/R) injury, and the potential molecular mechanisms.
  
  
  METHODS
  Rats were randomly divided into sham, model with cerebral I/R injury, or HT-treated groups, then administered orally with vehicle (for the sham and model group) or HT (0.5, 1.0, or 2.0 mg/kg) respectively, for 3 or 7 days. Functional recovery was assessed by cylinder test, beam walking test, and adhesive test. Neurogenesis was investigated by double immunofluorescence staining for 5-ethynyl-2-deoxyuridine (EdU) and neuronal nuclear protein (NeuN). The proteins of kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were assayed by western blotting. The level of BDNF mRNA was evaluated by RT-PCR.
  
  
  RESULTS
  Compared with the model group, treatment with HT significantly promoted functional recovery in I/R injured rats (p < 0.05 or p < 0.01). The generation of new neurons was increased in the HT groups. HT treatment for 3 days increased the level of BDNF mRNA in I/R injured rats. Expression of PKA, phosphorylated CREB, and BDNF were significantly (p < 0.05) increased with the 7-day HT treatment.
  
  
  CONCLUSIONS
  These results indicated that HT treatment could promote functional recovery after stroke. HT enhanced the expression of BDNF and increased the level of neurogenesis in cerebral I/R animal, which might be associated with the functional recovery.
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Duan
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Chengwen
authors.initials: C
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Yantai, 264005, People's Republic of China. fufenghua@sohu.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. fufenghua@sohu.com.
authors.forename: Fenghua
authors.identifier: http://orcid.org/0000-0002-5659-013X
authors.initials: F
authors.lastname: Fu
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020521:Stroke / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal
keywords: Cerebral ischemia-reperfusion; Functional recovery; Huatuo Zaizao pill; Neurogenesis; Stroke