Knockdown of C-C chemokine receptor 5 (CCR5) is protective against cerebral ischemia and reperfusion injury.
Research paper by
Edna Constanza Gómez EC Victoria, Eliana Cristina EC de Brito Toscano, Ana Clara AC de Sousa Cardoso, Daniele Gonçalves DG da Silva, Aline Silva AS de Miranda, Lucíola L da Silva Barcelos, Michelle Adriane MA Sugimoto, Lirlândia Pires LP Sousa, Isabel Vieira IV de Assis Lima, Antônio Carlos Pinheiro AC de Oliveira, Fátima F Brant, Fabiana Simão FS Machado, Mauro Martins MM Teixeira, Antônio Lúcio AL Teixeira, Milene Alvarenga MA Rachid
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 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.