title: Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.
abstract: OBJECTIVE
  Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke.
  
  
  METHODS
  Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias.
  
  
  RESULTS
  We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate.
  
  
  CONCLUSIONS
  This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Mei-Xue
authors.initials: MX
authors.lastname: Dong
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Hu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shen
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Jun-Xi
authors.initials: JX
authors.lastname: Pan
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: You-Dong
authors.initials: YD
authors.lastname: Wei
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yi-Yun
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Ren
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: Liang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Zhao
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.|Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000139:chemically induced / Q000150:complications; D002544:Cerebral Infarction / Q000150:complications* / Q000188:drug therapy; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D020521:Stroke / Q000150:complications* / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator