Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury.
Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury.
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DOI：
10.1111/j.1471-4159.2009.06190.x
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发表时间：
2009-07
影响因子：
4.7
通讯作者：
Bethea JR
中科院分区：
文献类型：
--
作者：
Brambilla R;Hurtado A;Persaud T;Esham K;Pearse DD;Oudega M;Bethea JR
我们先前表明，星形胶质细胞中核因子 - κB（NF - κB）失活会导致脊髓损伤（SCI）后功能恢复改善。这与促炎介质和硫酸软骨素蛋白聚糖表达降低以及白质保留增加相关。因此我们假设星形胶质细胞NF - κB失活会为轴突萌发和再生创造一个更有利的环境。我们在胶质纤维酸性蛋白 - IκBα - 显性负性（GFAP - IκBα - dn）小鼠和野生型（WT）小鼠中诱导挫伤性和完全横断性脊髓损伤，并在损伤8周后进行逆行（荧光金）和顺行（生物素化葡聚糖胺）示踪。在挫伤性脊髓损伤后，在转基因小鼠的运动皮层、网状结构和中缝核中发现了更多荧光金标记的细胞。在GFAP - IκBα - dn小鼠中，在损伤尾侧发现了保留的和萌发的生物素化葡聚糖胺阳性皮质脊髓轴突。在GFAP - IκBα - dn小鼠中，在损伤紧邻头侧检测到更多荧光金标记的神经元，同时突触和轴突生长相关分子的表达增加。然而，在横断后，在两种基因型小鼠中，分别在损伤头侧和尾侧均未发现荧光金标记的神经元或充满生物素化葡聚糖胺的轴突。这些数据表明，抑制星形胶质细胞NF - κB会产生一种促进生长的环境，促进对运动至关重要的脊髓上和脊髓固有回路的保留和萌发，而非再生，从而有助于GFAP - IκBα - dn小鼠在脊髓损伤后观察到的功能恢复改善。
We previously showed that NF-κB inactivation in astrocytes leads to improved functional recovery following spinal cord injury (SCI). This correlated with reduced expression of pro-inflammatory mediators and chondroitin sulphate proteoglycans, and increased white matter preservation. Hence we hypothesized that inactivation of astrocytic NF-κB would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-IκBα-dn and WT mice and performed retrograde (fluorogold) and anterograde (biotinylated dextran amine) tracing eight weeks after injury. Following contusive SCI, more fluorogold-labeled cells were found in motor cortex, reticular formation, and raphe nuclei of transgenic mice. Spared and sprouting biotinylated dextran amine-positive corticospinal axons were found caudal to the lesion in GFAP-IκBα-dn mice. Higher numbers of fluorogold-labeled neurons were detected immediately rostral to the lesion in GFAP-IκBα-dn mice, accompanied by increased expression of synaptic and axonal growth-associated molecules. After transection, however, no fluorogold-labeled neurons or biotinylated dextran amine-filled axons were found rostral and caudal to the lesion, respectively, in either genotype. These data demonstrated that inhibiting astroglial NF-κB resulted in a growth-supporting terrain promoting sparing and sprouting, rather than regeneration, of supraspinal and propriospinal circuitries essential for locomotion, hence contributing to the improved functional recovery observed after SCI in GFAP-IκBα-dn mice.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
2.5
作者：
Gerasimenko, Yury P.;Ichiyama, Ronaldo M.;Edgerton, V. Reggie
通讯作者：
Edgerton, V. Reggie
影响因子：
--
作者：
Dusart, I;Ghoumari, A;Sotelo, C
通讯作者：
Sotelo, C
影响因子：
3.4
作者：
Fabes, Jez;Anderson, Patrick;Bolsover, Stephen
通讯作者：
Bolsover, Stephen
软骨素酶ABC促进脊髓损伤后完整和受伤的脊柱系统的发芽。
DOI：
10.1523/jneurosci.2980-06.2006
发表时间：
2006-10-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barritt AW;Davies M;Marchand F;Hartley R;Grist J;Yip P;McMahon SB;Bradbury EJ
通讯作者：
Bradbury EJ