Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited ...Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase （MMP） dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at Ts, and 5 mm of spinal cord was removed （group T）. In group R, spinal cord-transected rats received treatment with fibroblast grow th factor- 1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 （an MMP inhibitor） to the fibrin mix. We found that MMP-9, but not MMP- 2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 （M2 macrophage subset）/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS^＋ cells and that the migration of the arginase-1^＋ population could be regulated locally. Simultaneous application of MMP in- hibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.展开更多
Kava or kava-kava （Piper methysticum） is a plant used for the production of a ritual drink with tranquilizing properties. The kavalactones are the main compounds of the kava drinks （see Table 1 for names and struct...Kava or kava-kava （Piper methysticum） is a plant used for the production of a ritual drink with tranquilizing properties. The kavalactones are the main compounds of the kava drinks （see Table 1 for names and structures of the main kavalactones）. There are many clinical trials on the use of kava product for anti-anxiety, and a systematic review supports the use of kava for the treatment of generalized anxiety （Sarris et al., 2009）. Adverse effects on the liver have been reported, and kava is regulated in a number of countries （Teschke, 2010）.展开更多
This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promo...This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promoted survival of neuronal and oligodendroglial cells but effectively reduced LPS stimulation in spinal cord cultures. We further utilized the NYU weight-drop device to induce contusive spinal cord injury (SCI) in rats. Immediately after dropping the impactor from a height of 25 mm onto thoracic spinal segment, MCM was intrathecally administered. At 6 weeks post-injury, SCI rats receiving MCM > 50 kDa treatment showed significant hind-limb improvement over MCM 50 kDa, of microglia was neuroprotective against spinal cord injury.展开更多
基金supported by the National Science Council(102-2320-B-324-001),Chinaupported by grants from Taipei Veterans General Hospital(V103E6-001&V104E6-001)by grants(MOST 104-2314-B-010-012-MY3,MOST 105-2314-B-010-013-MY2 and MOST 106-2632-B-324-001)from the Ministry of Science and Technology in Taiwan,China
文摘Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase （MMP） dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at Ts, and 5 mm of spinal cord was removed （group T）. In group R, spinal cord-transected rats received treatment with fibroblast grow th factor- 1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 （an MMP inhibitor） to the fibrin mix. We found that MMP-9, but not MMP- 2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 （M2 macrophage subset）/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS^＋ cells and that the migration of the arginase-1^＋ population could be regulated locally. Simultaneous application of MMP in- hibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.
基金supported by the grants from the Ministry of Science and Technology,Taiwan,China(formerly National Science Council Taiwan)(NSC 99-2811-M-324-003,NSC 101-2320-B-324-001)
文摘Kava or kava-kava （Piper methysticum） is a plant used for the production of a ritual drink with tranquilizing properties. The kavalactones are the main compounds of the kava drinks （see Table 1 for names and structures of the main kavalactones）. There are many clinical trials on the use of kava product for anti-anxiety, and a systematic review supports the use of kava for the treatment of generalized anxiety （Sarris et al., 2009）. Adverse effects on the liver have been reported, and kava is regulated in a number of countries （Teschke, 2010）.
文摘This work examines whether microglia-conditioned medium (MCM) is beneficial in stressed spinal cord cells or tissues. MCM was separated into two fractions by 50 kDa molecular cut-off centrifugation. MCM not only promoted survival of neuronal and oligodendroglial cells but effectively reduced LPS stimulation in spinal cord cultures. We further utilized the NYU weight-drop device to induce contusive spinal cord injury (SCI) in rats. Immediately after dropping the impactor from a height of 25 mm onto thoracic spinal segment, MCM was intrathecally administered. At 6 weeks post-injury, SCI rats receiving MCM > 50 kDa treatment showed significant hind-limb improvement over MCM 50 kDa, of microglia was neuroprotective against spinal cord injury.
