title: Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke.
abstract: Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals.
authors.affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut, India.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Davis
authors.affiliation: Statistical Services Unit, University of Sheffield, Sheffield, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Laud
authors.affiliation: Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
authors.forename: Zsanett
authors.initials: Z
authors.lastname: Bahor
authors.affiliation: School of Biotechnology, National Institute of Technology Calicut, Calicut, India rajanikant@nitc.ac.in arshad.majid@sheffield.ac.uk.
authors.forename: G K
authors.initials: GK
authors.lastname: Rajanikant
authors.affiliation: Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
authors.forename: Arshad
authors.initials: A
authors.lastname: Majid
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002336:Carnosine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D002336:Carnosine
keywords: Carnosine; ischemic stroke; meta-analysis; neuroprotection; systematic review