Recovery from chronic spinal cord contusion after Nogo receptor intervention.
Recovery from chronic spinal cord contusion after Nogo receptor intervention.
复制标题
DOI：
10.1002/ana.22527
复制
发表时间：
2011-11
影响因子：
11.2
通讯作者：
Strittmatter, Stephen M.
中科院分区：
文献类型：
--
作者：
Wang, Xingxing;Duffy, Philip;McGee, Aaron W.;Hasan, Omar;Gould, Grahame;Tu, Nathan;Harel, Noam Y.;Huang, Yiyun;Carson, Richard E.;Weinzimmer, David;Ropchan, Jim;Benowitz, Larry I.;Cafferty, William B. J.;Strittmatter, Stephen M.
几种干预措施在CNS损伤后不久启动时促进轴突生长和功能恢复，包括用可溶性Nogo受体（NgR 1，RTN 4 R）“诱饵”蛋白阻断髓鞘衍生的抑制剂。我们研究了这种干预在更普遍和难治性慢性脊髓损伤中的疗效。我们在脊髓半切损伤后8周开始通过条件性基因靶向在小鼠中遗传性地消除NgR 1通路，并在随后的4个月内通过视频运动学监测开放场地中的运动。在单独的药理学实验中，脊髓挫伤后3个月开始鞘内NgR 1诱饵蛋白给药。在挫伤后4至6个月的3个月治疗期间评估了运动和中缝脊髓轴突生长。慢性状态下NgR 1的条件性缺失导致运动功能的逐渐改善，伴随着尾侧脊髓中缝脊神经轴突密度的增加。在慢性大鼠脊髓挫伤中，损伤后4-6个月的NgR 1诱饵治疗导致29%（35只中的10只）的大鼠恢复负重状态，而对照组大鼠为0%（29只中的0只）（P<0.05）。开放视野BBB运动评分显示NgR处理组相对于对照组的显著改善（P<0.005，重复测量ANOVA）。通过免疫组织学和使用5-羟色胺再摄取配体的正电子发射断层扫描，在NgR 1-诱饵处理的动物中检测到损伤尾侧中缝脊神经轴突密度的增加。用NgR 1诱饵拮抗髓磷脂衍生的抑制剂信号传导增强慢性脊髓损伤的恢复
Several interventions promote axonal growth and functional recovery when initiated shortly after CNS injury, including blockade of myelin-derived inhibitors with soluble Nogo Receptor (NgR1, RTN4R) ‘decoy’ protein. We examined the efficacy of this intervention in the much more prevalent and refractory condition of chronic spinal cord injury. We eliminated the NgR1 pathway genetically in mice by conditional gene targeting starting 8 weeks after spinal hemisection injury and monitored locomotion in the open field and by video kinematics over the ensuing 4 months. In a separate pharmacological experiment, intrathecal NgR1 decoy protein administration was initiated 3 months after spinal cord contusion injury. Locomotion and raphespinal axon growth were assessed during 3 months of treatment between 4 and 6 months after contusion injury. Conditional deletion of NgR1 in the chronic state results in gradual improvement of motor function accompanied by increased density of raphespinal axons in the caudal spinal cord. In chronic rat spinal contusion, NgR1 decoy treatment from 4–6 months after injury results in 29% (10 of 35) of rats recovering weight-bearing status compared to 0% (0 of 29) of control rats (P<0.05). Open field BBB locomotor scores showed a significant improvement in the NgR-treated group relative to the control group (P<0.005, repeated measures ANOVA). An increase in raphespinal axon density caudal to the injury is detected in NgR1-decoy-treated animals by immunohistology and by positron emission tomography using a serotonin reuptake ligand. Antagonizing myelin-derived inhibitors signaling with NgR1 decoy augments recovery from chronic spinal cord injury.
登录
查看更多内容
影响因子：
5.3
作者：
Fournier, AE;Takizawa, BT;Strittmatter, SM
通讯作者：
Strittmatter, SM
影响因子：
4.2
作者：
Cao, Y.;Shumsky, J. S.;Murray, M.
通讯作者：
Murray, M.
DOI：
10.1523/jneurosci.5885-08.2009
发表时间：
2009-05-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Harvey PA;Lee DH;Qian F;Weinreb PH;Frank E
通讯作者：
Frank E
影响因子：
82.9
作者：
Courtine, Gregoire;Song, Bingbing;Sofroniew, Michael V.
通讯作者：
Sofroniew, Michael V.
影响因子：
5.3
作者：
Fischer, D;He, ZG;Benowitz, LI
通讯作者：
Benowitz, LI