title: Epidermal growth factor and growth hormone-releasing peptide-6: combined therapeutic approach in experimental stroke.
abstract: OBJECTIVE
  Stroke is the second cause of mortality worldwide, with a high incidence of disability in survivors. Promising candidate drugs have failed in stroke trials. Combined therapies are attractive strategies that simultaneously target different points of stroke pathophysiology. The aim of this work is to determine whether the combined effects of epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP6) can attenuate clinical signs and pathology in an experimental stroke model.
  
  
  METHODS
  Brain global ischemia was generated in Mongolian gerbils by 15 minutes of carotid occlusion. After reperfusion, EGF, GHRP6 or EGF+GHRP6 were intraperitoneally administered. Clinical manifestations were monitored daily. Three days after reperfusion, animals were anesthetized and perfused with an ink solution. The anatomy of the Circle of Willis was characterized. Infarct volume and neuronal density were analyzed.
  
  
  RESULTS
  EGF+GHRP6 co-administration reduced clinical manifestations and infarct volume and preserved neuronal density. No correlation was observed between the grade of anastomosis of the Circle of Willis and clinical manifestations in the animals receiving EGF+GHRP6, as opposed to the vehicle-treated gerbils.
  
  
  CONCLUSIONS
  Co-treatment with EGF and GHRP6 affects both the clinical and pathological outcomes in a global brain ischemia model, suggesting a suitable therapeutic approach for the acute management of stroke.
authors: Center for Genetic Engineering and Biotechnology, Pharmaceutical Division, Cubanacan, Playa, La Habana, Cuba. diana.garcia@cigb.edu.cu
authors: Diana
authors: D
authors: García Del Barco-Herrera
authors: Nelvys Subirós
authors: NS
authors: Martínez
authors: Rosa María
authors: RM
authors: Coro-Antich
authors: Jorge Martín
authors: JM
authors: Machado
authors: José Suárez
authors: JS
authors: Alba
authors: Sandra Rodríguez
authors: SR
authors: Salgueiro
authors: Jorge Berlanga
authors: JB
authors: Acosta
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002941:Circle of Willis / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000627:therapeutic use*; D005849:Gerbillinae; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D004815:Epidermal Growth Factor