Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury.
Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury.
复制标题
减少周细胞来源的瘢痕促进脊髓损伤后的恢复。
DOI：
10.1016/j.cell.2018.02.004
复制
发表时间：
2018-03-22
期刊：
影响因子：
64.5
通讯作者：
Frisén J
中科院分区：
文献类型：
--
作者：
Dias DO;Kim H;Holl D;Werne Solnestam B;Lundeberg J;Carlén M;Göritz C;Frisén J
中枢神经系统损伤常常切断轴突。在病变部位局部形成的瘢痕组织被认为会阻碍轴突再生，导致永久性功能缺陷。我们报告，通过抑制周细胞的一个亚类的后代的产生，导致脊髓损伤后的小鼠纤维化和细胞外基质沉积减少。在具有减弱的周细胞源性瘢痕形成的动物中，脊髓损伤后中缝脊束和皮质脊髓束轴突的再生增强，感觉运动功能恢复改善。利用光遗传学刺激，我们证明了再生的皮质脊髓束轴突整合到病变部位下方的局部脊髓回路中。再生轴突的数量与感觉运动功能恢复的改善相关。总之，周细胞源性纤维化的衰减代表了促进CNS损伤后恢复的有前景的治疗方法。抑制周细胞增殖减少损伤后的纤维化瘢痕组织减弱的周细胞来源的瘢痕形成促进运动轴突再生的轴突功能性地重新整合到局部脊髓回路中减弱的周细胞来源的瘢痕形成改善感觉运动恢复通过一个亚组的周细胞减弱纤维化组织的产生促进肾上腺素能和皮质脊髓束轴突的再生并改善脊髓损伤后的功能恢复。
CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury. Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury Attenuated pericyte-derived scarring facilitates motor axon regeneration Regenerated axons functionally re-integrate into the local spinal circuitry Attenuated pericyte-derived scarring improves sensorimotor recovery Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.6
作者：
He L;Vanlandewijck M;Raschperger E;Andaloussi Mäe M;Jung B;Lebouvier T;Ando K;Hofmann J;Keller A;Betsholtz C
通讯作者：
Betsholtz C
影响因子：
23.9
作者：
Guimarães-Camboa N;Cattaneo P;Sun Y;Moore-Morris T;Gu Y;Dalton ND;Rockenstein E;Masliah E;Peterson KL;Stallcup WB;Chen J;Evans SM
通讯作者：
Evans SM
影响因子：
16.2
作者：
Arenkiel, Benjamin R.;Peca, Joao;Feng, Guoping
通讯作者：
Feng, Guoping
影响因子：
14.5
作者：
Buss, Armin;Pech, Katrin;Brook, Gary A.
通讯作者：
Brook, Gary A.