Stromal cell-derived factor-1 alpha promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats.

ABSTRACT

Stromal cell-derived factor (SDF)-1alpha is involved in the trafficking of hematopoietic stem cells from bone marrow to peripheral blood, and its expression is increased in the penumbra of the ischemic brain. In this study, SDF-1alpha was found to exert neuroprotective effects that rescued primary cortical cultures from H(2)O(2) neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1alpha showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1alpha injection enhanced the targeting of bone marrow (BM)-derived cells to the injured brain, as demonstrated in green fluorescent protein-chimeric mice with cerebral ischemia. In addition, increased vascular density in the ischemic cortex of SDF-1alpha-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1alpha resulted in neuroprotection against neurotoxic insult, and it induced increased BM-derived cell targeting to the ischemic brain, thereby reducing the volume of cerebral infarction and improving neural plasticity.