Xiaohui Lin1,2,3,4, Hongbin Chen1,2,3,4, Manli Chen1,2,3,4, Ting Li1,2,3,4, Yongxing Lai1,2,3,4, Longzai Lin1,2,3,4, Peiqiang Lin1,2,3,4, Ji Liu1,2,3,4, Yixian Zhang1,2,3,4, Ronghua Chen1,2,3,4, Houwei Du1,2,3,4, Xinhong Jiang1,2,3,4, Nan Liu5,6,7,8. 1. Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China. 2. Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China. 3. Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China. 4. Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China. 5. Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China. xieheliunan1984@sina.com. 6. Department of Rehabilitation, Fujian Medical University Union Hospital, Fuzhou, China. xieheliunan1984@sina.com. 7. Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China. xieheliunan1984@sina.com. 8. Institute of Clinical Neurology, Fujian Medical University, Fuzhou, China. xieheliunan1984@sina.com.
Abstract
BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats. METHODS: A cerebral ischemic rat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1 × 106 in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3β, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence. RESULTS: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3β and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT. CONCLUSION: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3β/CRMP-2 signaling pathway.
BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats. METHODS: A cerebral ischemicrat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1 × 106 in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3β, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence. RESULTS: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3β and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT. CONCLUSION: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3β/CRMP-2 signaling pathway.
Authors: S R McIver; M Muccigrosso; E R Gonzales; J M Lee; M S Roberts; M S Sands; M P Goldberg Journal: Neuroscience Date: 2010-05-31 Impact factor: 3.590