The effects of bone marrow mononuclear cells on neurodegeneration after ischemia in mice

Abstract

Objective To investigate the effects of bone marrow mononuclear cells (BMMNCs) on neurodegeneration after cerebral ischemia in mice. Methods Adult male mice were randomly divided into PBS treated group and BMMNCs treated group. The model was established with suture emboli method; BMMNCs were isolated with density gradient centrifugation method.The production of cytokines from BMMNCs including interleukin-10 (IL-10), vascular endothelial growth factor (VEGF) and insulinlike growth factor-I (IGF-1) were tested by enzyme-linked immunosorbent assay (ELISA) under normoxic or hypoxic conditions.Mice were injected with PBS or BMMNCs via tail vein 6 h after ischemia reperfusion.Neurological functional deficits, the activity of microglial cell and neurodegenration were assessed on day 1, 4, 7 after MCAO, and infarct volume was assessed on day 7. Results (1) Compared with BMMNCs under normoxic conditions, BMMNCs under hypoxic conditions secreted more IL-10, VEGF, IGF-1 after 24h of cultivation(P<0.05). (2) BMMNCs transplantation significantly reduced neurologic functional deficits and the number of activated microglia and degenerated neurons on days 4, 7 compared with PBS treated groups (P<0.05). (3) Compared with PBS treated group((37.1±6.9)%), BMMNCs transplantation significantly reduced infarct volume((27.8±7.5)%)(P<0.05). Conclusion Bone marrow mononuclear cells can significantly inhibit neurodegeneration, promote neurological recover and reduce infarct volume through inhibition of microglial cell activation by secretion of cytokines including IL-10, VEGF and IGF-1. Key words: Ischemic stroke; Bone marrow mononuclear cells; Cell transplantation; Cytokines; Microglia; Neurodegeneration