Background::Our previous studies showed that topical application of mesenchymal stem cells (MSCs) improved functional recovery in rat traumatic brain injury (TBI) model, and hypoxic precondition further enhanced the therapeutic effects of MSCs. There was no previous study on the attenuation of cerebral edema by MSCs. We investigated whether topical application of normoxic and hypoxic MSCs could reduce cerebral edema in an experimental TBI model.Methods::Two million normoxic (n N = 24) and hypoxic (n N = 24) MSCs were applied topically to exposed the cerebral cortex in a controlled cortical impact (CCI) model. The MSCs were fixed in position with fibrin glue. No treatment was given to control animals (TBI only: n n = 24). After surgery, four animals in each group were sacrificed daily (day 1 to day 6) for edema evaluation. Normal animals without TBI were used as reference (n n = 4). The expressions of GFAP, AQP4, and MMP9 were also investigated by immunofluorescence staining and RT-PCR at day 3.n Results::The edema peaked within 3 days after TBI. Compared with the control, hypoxic MSCs reduced brain water content significantly (n p < 0.05). Both hypoxic and normoxic MSCs downregulated the expression of MMP9 and normalized AQP4 distribution to astrocyte end feet.n Conclusion::Our preliminary study showed that topical application of hypoxic MSCs suppressed both vasogenic and cytotoxic edema formation.“,”Background::Our previous studies showed that topical application of mesenchymal stem cells (MSCs) improved functional recovery in rat traumatic brain injury (TBI) model, and hypoxic precondition further enhanced the therapeutic effects of MSCs. There was no previous study on the attenuation of cerebral edema by MSCs. We investigated whether topical application of normoxic and hypoxic MSCs could reduce cerebral edema in an experimental TBI model.Methods::Two million normoxic (n N = 24) and hypoxic (n N = 24) MSCs were applied topically to exposed the cerebral cortex in a controlled cortical impact (CCI) model. The MSCs were fixed in position with fibrin glue. No treatment was given to control animals (TBI only: n n = 24). After surgery, four animals in each group were sacrificed daily (day 1 to day 6) for edema evaluation. Normal animals without TBI were used as reference (n n = 4). The expressions of GFAP, AQP4, and MMP9 were also investigated by immunofluorescence staining and RT-PCR at day 3.n Results::The edema peaked within 3 days after TBI. Compared with the control, hypoxic MSCs reduced brain water content significantly (n p < 0.05). Both hypoxic and normoxic MSCs downregulated the expression of MMP9 and normalized AQP4 distribution to astrocyte end feet.n Conclusion::Our preliminary study showed that topical application of hypoxic MSCs suppressed both vasogenic and cytotoxic edema formation.