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
Conclusion: Taken together, our results suggest a potential neuroprotection in the absence of CCR5
receptor during global brain ischemia and reperfusion injury.