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Assessment of dose-effect and therapeutic time window in preclinical studies of rhEGF and GHRP-6 coadministration for stroke therapy.
Subirós, Nelvys; Pérez-Saad, Héctor M; Berlanga, Jorge A; Aldana, Lizet; García-Illera, Gerardo; Gibson, Claire L; García-Del-Barco, Diana.
Afiliação
  • Subirós N; a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
  • Pérez-Saad HM; a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
  • Berlanga JA; a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
  • Aldana L; a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
  • García-Illera G; b Group of Stability and Reference Materials , Quality Control Division, Center for Genetic Engineering and Biotechnology , Havana , Cuba.
  • Gibson CL; c School of Psychology , University of Leicester , UK.
  • García-Del-Barco D; a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
Neurol Res ; 38(3): 187-95, 2016 Mar.
Article em En | MEDLINE | ID: mdl-26311576
BACKGROUND: Stroke continues to be a leading cause of mortality and morbidity worldwide, and novel therapeutic options for ischaemic stroke are urgently needed. In this context, drug combination therapies seem to be a viable approach, which has not been fully explored in preclinical studies. OBJECTIVES: In this work, we assessed the dose-response relationship and therapeutic time window, in global brain ischaemia, of a combined therapeutic approach of recombinant human epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP-6). METHODS: Mongolian gerbils underwent 15 minutes occlusion of both common carotid arteries. Four different doses of rhEGF, GHRP-6 and these combined agents were intraperitoneally administered immediately after the onset of reperfusion. Having identified a better response with both agents, rhEGF+GHRP-6 were administered at 2, 4, 6, 8 or 24 hours after the onset of reperfusion to assess the time window of effectiveness. Animals were evaluated daily for neurological deficits. Three days post-occlusion, the animals were sacrificed and 2,3,5-triphenyltetrazolium chloride was used to quantify infarcted tissues. RESULTS: The coadministration of rhEGF and GHRP-6 at doses of 100 and 600 µg/kg, respectively, administered up to 4 hours following the ischaemic insult, significantly improved survival and neurological outcome, and reduced infarct volume compared with vehicle treatment. These results are considered as an additional proof of concept as supporting a combined therapeutic approach and justify the further development of this preclinical research.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Acidente Vascular Cerebral / Avaliação Pré-Clínica de Medicamentos / Fator de Crescimento Epidérmico Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Neurol Res Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Cuba País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Acidente Vascular Cerebral / Avaliação Pré-Clínica de Medicamentos / Fator de Crescimento Epidérmico Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Neurol Res Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Cuba País de publicação: Reino Unido