title: Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury.
abstract: Stroke is the second leading cause of death and a major cause of disability of adults worldwide. Inflammatory processes are known to contribute to the pathophysiology of cerebral ischemia, especially following reperfusion. Chemokines and their receptors are involved in migration of leukocytes and have been implicated in the pathogenesis of ischemic stroke.
  
  
  
  In the present study, we investigated the effects of C-C chemokine receptor type 5 (CCR5) deficiency on neurological outcome, brain damage and expression of pro-inflammatory chemokines: chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (CC motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5), and the brain-derived neurotrophic factor (BDNF).
  
  
  
  Adult male C57BL/6 (wild-type) (WT) and CCR5 deficient mice were subjected to transient cerebral ischemia induced by 25 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 hours of reperfusion. Mice were divided into four groups: WT sham group, which underwent sham operation; WT ischemic group, which was subjected to transient bilateral common carotid artery occlusion, CCR5-/- sham group, which underwent sham operation, and CCR5-/- ischemic group, which was subjected to transient BCCAO.
  
  
  
  In CCR5 deficiency, we observed a significant improvement in the neurological deficits associated with decreased brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, CCR5 deficiency revealed decreased percentage of necrotic cavities areas and frequency of ischemic neurons by histometric analysis. In addition, CCR5-/- ischemic animals showed lower brain levels of the chemokine CXCL1 and higher levels of BDNF by ELISA, compared with WT BCCAo mice.
  
  
  
  Taken together, our results suggest a potential neuroprotection in the absence of CCR5 receptor during global brain ischemia and reperfusion injury.
authors.affiliation: Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Edna Constanza Gómez
authors.initials: ECG
authors.lastname: Victoria
authors.affiliation: Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Eliana Cristina
authors.initials: EC
authors.lastname: de Brito Toscano
authors.affiliation: Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Ana Clara
authors.initials: AC
authors.lastname: de Sousa Cardoso
authors.affiliation: Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Daniele Gonçalves
authors.initials: DG
authors.lastname: da Silva
authors.affiliation: Departamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Aline Silva
authors.initials: AS
authors.lastname: de Miranda
authors.affiliation: Departamento de Fisiologia e Biofísica, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Lucíola
authors.initials: L
authors.lastname: da Silva Barcelos
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Michelle Adriane
authors.initials: MA
authors.lastname: Sugimoto
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Lirlândia Pires
authors.initials: LP
authors.lastname: Sousa
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas (ICB), Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Isabel Vieira
authors.initials: IV
authors.lastname: de Assis Lima
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas (ICB), Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Antônio Carlos Pinheiro
authors.initials: ACP
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Brant
authors.affiliation: Departamento de Bioquímica e Imunologia,Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Fabiana Simao
authors.initials: FS
authors.lastname: Machado
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Farmácia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX. United States.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Universidade Federal de Minas Gerais, Instituto de Ciencias Biologicas. Departamento de Patologia Geral. Laboratorio de Apoptose. Campus Pampulha, Av. Antonio Carlos 6.627 - Belo Horizonte, Minas Gerais. Brazil.
authors.forename: Milene Alvarenga
authors.initials: MA
authors.lastname: Rachid
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D009460:Neurologic Examination; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000592874:CCR5 protein, mouse; D016207:Cytokines; D009414:Nerve Growth Factors; D019713:Receptors, CCR5
keywords: BDNF; Brain; CCR5; chemokines; ischemia; mice; reperfusion