PMID- 28294064 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20180924 IS - 1875-5739 (Electronic) IS - 1567-2026 (Linking) VI - 14 IP - 2 DP - 2017 TI - Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury. PG - 125-131 LID - 10.2174/1567202614666170313113056 [doi] AB - BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Taken together, our results suggest a potential neuroprotection in the absence of CCR5 receptor during global brain ischemia and reperfusion injury. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Victoria, Edna Constanza Gomez AU - Victoria ECG AD - Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - de Brito Toscano, Eliana Cristina AU - de Brito Toscano EC AD - Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - de Sousa Cardoso, Ana Clara AU - de Sousa Cardoso AC AD - Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - da Silva, Daniele Goncalves AU - da Silva DG AD - Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - de Miranda, Aline Silva AU - de Miranda AS AD - Departamento de Morfologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - da Silva Barcelos, Luciola AU - da Silva Barcelos L AD - Departamento de Fisiologia e Biofisica, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Sugimoto, Michelle Adriane AU - Sugimoto MA AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Sousa, Lirlandia Pires AU - Sousa LP AD - Departamento de Analises Clinicas e Toxicologicas, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - de Assis Lima, Isabel Vieira AU - de Assis Lima IV AD - Departamento de Farmacologia, Instituto de Ciencias Biologicas (ICB), Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - de Oliveira, Antonio Carlos Pinheiro AU - de Oliveira ACP AD - Departamento de Farmacologia, Instituto de Ciencias Biologicas (ICB), Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Brant, Fatima AU - Brant F AD - Departamento de Bioquimica e Imunologia, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Machado, Fabiana Simao AU - Machado FS AD - Departamento de Bioquimica e Imunologia,Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Teixeira, Mauro Martins AU - Teixeira MM AD - Departamento de Bioquimica e Imunologia, Faculdade de Farmacia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG. Brazil. FAU - Teixeira, Antonio Lucio AU - Teixeira AL AD - Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX. United States. FAU - Rachid, Milene Alvarenga AU - Rachid MA AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United Arab Emirates TA - Curr Neurovasc Res JT - Current neurovascular research JID - 101208439 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (CCR5 protein, mouse) RN - 0 (Cytokines) RN - 0 (Nerve Growth Factors) RN - 0 (Receptors, CCR5) SB - IM MH - Animals MH - Brain/pathology MH - Brain Ischemia/genetics/*metabolism/*therapy MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cytokines/genetics/metabolism MH - Disease Models, Animal MH - Gene Expression Regulation/*genetics/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nerve Growth Factors/metabolism MH - Neurologic Examination MH - Receptors, CCR5/*deficiency/genetics MH - Reperfusion Injury/genetics/*metabolism/*therapy OTO - NOTNLM OT - BDNF OT - Brain OT - CCR5 OT - chemokines OT - ischemia OT - mice OT - reperfusion EDAT- 2017/03/16 06:00 MHDA- 2018/03/23 06:00 CRDT- 2017/03/16 06:00 PHST- 2016/10/17 00:00 [received] PHST- 2017/02/16 00:00 [revised] PHST- 2017/02/17 00:00 [accepted] PHST- 2017/03/16 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2017/03/16 06:00 [entrez] AID - CNR-EPUB-82246 [pii] AID - 10.2174/1567202614666170313113056 [doi] PST - ppublish SO - Curr Neurovasc Res. 2017;14(2):125-131. doi: 10.2174/1567202614666170313113056.