Brain-derived CCR5 Contributes to Neuroprotection and Brain Repair after Experimental Stroke

Chemokine (C-C motif) receptor 5 (CCR5) is expressed not only in the immune cells but also in cerebral cells such as neurons, glia, and vascular cells. Stroke triggers high expression of CCR5 in the brain. However, the role of CCR5 in stroke remains unclear. In this study, using bone marrow chimeras we have determined the involvement of brain-derived or bone marrow-derived CCR5 in neuroprotection and brain repair after experimental stroke. CCR5(-/-) mice that received either wild-type (WT) or CCR5(-/-) bone marrow transplantation showed larger infarction sizes than the WT mice that received either WT or CCR5(-/-) bone marrow transplantation in both the acute (48h) and subacute (2 months) phases after cerebral cortical ischemia, suggesting that the lack of CCR5 in the brain leads to severe brain damage after stroke. However, the lack of CCR5 in the bone marrow-derived cells did not affect infarction size. The impairments of somatosensory-motor function and motor coordination were exacerbated in the mice lacking CCR5 in the brain. At 2 months poststroke, increased degenerative neurons, decreased dendrites and synapses, decreased Iba1(+) microglia/macrophages, reduced myelination and CNPase(+) oligodendrocytes in the peri-infarct cortex were observed in the mice lacking CCR5 in the brain. These pathological changes are significantly correlated with the increased infarction size and exacerbated neurological deficits. These data suggest that brain-derived CCR5 plays a key role in neuroprotection and brain repair in the subacute phase of stroke. This study reveals a novel role of CCR5 in stroke, which sheds new light on post-stroke pathomechanism.

Automated summary

The study reveals that brain-derived CCR5 plays a key role in neuroprotection and brain repair in the subacute phase of stroke. Lack of CCR5 in the brain leads to severe brain damage after stroke, while deficiency of CCR5 in bone marrow-derived cells does not affect infarction size.