After
stroke,
brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental
stroke. We show here that rats housed in EE after
stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory
cytokines in the ischemic core and the surrounding peri-
infarct area, including a significant reduction in the
stroke-induced
chemokine receptor CXCR4 and its natural
ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (
AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in
infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3(+)) and CD3(+)/CD4(+) T cells. Spleen
atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by
AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after
stroke contributes to depression of neurologic function after
stroke and that CXCR4 antagonism is beneficial for the recovery after
stroke.