Immature astrocytes promote CNS axonal regeneration when combined with chondroitinase ABC.
Immature astrocytes promote CNS axonal regeneration when combined with chondroitinase ABC.
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DOI：
10.1002/dneu.20820
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发表时间：
2010-10
影响因子：
3
通讯作者：
Silver, Jerry
中科院分区：
文献类型：
--
作者：
Filous, Angela R.;Miller, Jared H.;Coulson-Thomas, Yvette M.;Horn, Kevin P.;Alilain, Warren J.;Silver, Jerry
受损的成人中枢神经系统轴突的再生受到神经胶质疤痕形成的抑制。未成熟的星形胶质细胞能够支持强大的神经突生长并减少疤痕，因此，我们测试了这些细胞如果移植到脑损伤中是否会产生这种效果。利用体外斑点梯度模型重建神经胶质疤痕的强抑制性蛋白多糖环境，我们发现，单独的、未成熟但不成熟的星形胶质细胞在最具抑制性的外缘上形成桥梁的能力有限。反过来，星形胶质细胞桥可以促进成人感觉轴突跨梯度的重新生长。选择性酶抑制剂的使用表明，MMP-2 能够使未成熟的星形胶质细胞穿过蛋白聚糖边缘。通过软骨素酶 ABC 对斑点进行预处理，大大增强了未成熟神经胶质桥的桥构建过程和轴突再生。我们使用成年大鼠大脑扣带回的微损伤来测试基质修饰和未成熟星形胶质细胞在体内形成轴突再生桥梁的能力。通过 p75 免疫标记可视化受损的轴突，并对这些轴突再生的程度进行量化。与软骨素酶 ABC 共同注射的未成熟星形胶质细胞诱导病灶远端边缘以外的轴突再生。然而，当单独使用时，这两种治疗都不能促进轴突再生。我们的研究结果表明，当面对最小的病变时，在跨病变的适当桥存在且神经胶质疤痕中硫酸软骨素蛋白多糖（CSPG）水平降低的情况下，基底前脑的神经元可以再生。
Regeneration of injured adult CNS axons is inhibited by formation of a glial scar. Immature astrocytes are able to support robust neurite outgrowth and reduce scarring, therefore, we tested whether these cells would have this effect if transplanted into brain injuries. Utilizing an in vitro spot gradient model that recreates the strongly inhibitory proteoglycan environment of the glial scar we found that, alone, immature, but not mature, astrocytes had a limited ability to form bridges across the most inhibitory outer rim. In turn, the astrocyte bridges could promote adult sensory axon re-growth across the gradient. The use of selective enzyme inhibitors revealed that MMP-2 enables immature astrocytes to cross the proteoglycan rim. The bridge-building process and axon regeneration across the immature glial bridges were greatly enhanced by chondroitinase ABC pre-treatment of the spots. We used microlesions in the cingulum of the adult rat brains to test the ability of matrix modification and immature astrocytes to form a bridge for axon regeneration in vivo. Injured axons were visualized via p75 immunolabeling and the extent to which these axons regenerated was quantified. Immature astrocytes co-injected with chondroitinase ABC induced axonal regeneration beyond the distal edge of the lesion. However, when used alone, neither treatment was capable of promoting axonal regeneration. Our findings indicate that when faced with a minimal lesion, neurons of the basal forebrain can regenerate in the presence of a proper bridge across the lesion and when levels of chondroitin sulfate proteoglycans (CSPGs) in the glial scar are reduced.
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DOI：
10.1073/pnas.0900222106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Dray, Cyril;Rougon, Genevieve;Debarbieux, Franck
通讯作者：
Debarbieux, Franck
影响因子：
5.3
作者：
Andrews, Melissa R.;Czvitkovich, Stefan;Fawcett, James W.
通讯作者：
Fawcett, James W.
影响因子：
5.3
作者：
Fournier, AE;Takizawa, BT;Strittmatter, SM
通讯作者：
Strittmatter, SM
影响因子：
3.5
作者：
Duchossoy, Y;Horvat, JC;Stettler, O
通讯作者：
Stettler, O
影响因子：
14.5
作者：
Ibrahim, Ahmed G.;Kirkwood, Peter A.;Li, Ying
通讯作者：
Li, Ying