Matrix metalloproteinase-9 controls proliferation of NG2+ progenitor cells immediately after spinal cord injury.
Matrix metalloproteinase-9 controls proliferation of NG2+ progenitor cells immediately after spinal cord injury.
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DOI：
10.1016/j.expneurol.2011.06.015
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发表时间：
2011-10
影响因子：
5.3
通讯作者：
Shubayev, Veronica I.
中科院分区：
文献类型：
--
作者：
Liu, Huaqing;Shubayev, Veronica I.
我们已经证明，克服基质金属蛋白酶（MMP）介导的抑制胶质细胞增殖刺激轴突再生周围神经系统。成年CNS对损伤和脱髓鞘的再生能力取决于多能神经胶质NG 2+祖细胞增殖和成熟的能力，主要是少突胶质细胞。在此，我们已经建立了重要的作用，基质金属蛋白酶，特别是MMP-9，在调节NG 2+细胞增殖损伤的脊髓。在T9-10脊髓背侧半切后使用急性MMP-9/2抑制剂（SB-3CT）治疗短暂诱导MMP-9两天，产生NG 2+细胞有丝分裂的显著增加（通过溴脱氧尿苷掺入评估），但不产生GFAP+星形胶质细胞和Iba-1+小胶质细胞和/或巨噬细胞的有丝分裂。急性MMP-9/2阻断减少NG 2蛋白聚糖和N-甲基D-天冬氨酸（NMDA）受体NR 1亚基的脱落，其下降被认为伴随NG 2+细胞成熟为OL。急性MMP-9/2抑制后，有丝分裂后少突胶质细胞在髓鞘再生过程中的增加和半切脊髓中髓鞘神经病理学的改善伴随着运动和体感恢复。总的来说，这些数据确立了MMP在受损CNS中调节NG 2+细胞增殖的新作用，以及SCI后急性MMP-9阻断的长期益处。
We have demonstrated that overcoming matrix metalloproteinase (MMP)-mediated suppression of glial proliferation stimulates axonal regeneration in the peripheral nervous system. The regenerative capacity of the adult CNS in response to injury and demyelination depends on the ability of multipotent glial NG2+ progenitor cells to proliferate and mature, mainly into oligodendrocytes. Herein, we have established the important role of MMPs, specifically MMP-9, in regulation of NG2+ cell proliferation in injured spinal cord. Targeting transiently induced MMP-9 using acute MMP-9/2 inhibitor (SB-3CT) therapy for two days after T9-10 spinal cord dorsal hemisection produced a significant increase in mitosis (assessed by bromodeoxyuridine incorporation) of NG2+ cells but not GFAP+ astrocytes and Iba-1+ microglia and/or macrophages. Acute MMP-9/2 blockade reduced the shedding of the NG2 proteoglycan and of the NR1 subunit of the N-methyl D-aspartate (NMDA) receptor, whose decline is believed to accompany NG2+ cell maturation into OLs. Increase in post-mitotic oligodendrocytes during remyelination and improved myelin neuropathology in the hemisected spinal cord were accompanied by locomotion and somatosensory recovery after acute MMP-9/2 inhibition. Collectively, these data establish a novel role for MMPs in regulation of NG2+ cell proliferation in the damaged CNS, and a long-term benefit of acute MMP-9 block after SCI.
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DOI：
10.1523/jneurosci.6000-09.2010
发表时间：
2010-03-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
De Biase LM;Nishiyama A;Bergles DE
通讯作者：
Bergles DE
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
1.7
作者：
de Castro, R;Burns, CL;Romanic, AM
通讯作者：
Romanic, AM
影响因子：
3.5
作者：
Duchossoy, Y;Horvat, JC;Stettler, O
通讯作者：
Stettler, O
影响因子：
6.2
作者：
Lehmann, Helmar C.;Koehne, Angelika;Kieseier, Bernd C.
通讯作者：
Kieseier, Bernd C.