Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth
Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth
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DOI：
10.1089/neu.2007.0464
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发表时间：
2009-01-01
影响因子：
4.2
通讯作者：
Strittmatter, Stephen M.
中科院分区：
文献类型：
--
作者：
Wang, Xingxing;Budel, Stephane;Strittmatter, Stephen M.
GTP结合蛋白RhoA调节许多细胞类型中的微丝动力学，并介导髓鞘和硫酸软骨素蛋白聚糖对轴突再生的抑制。与大多数其他非甾体抗炎药不同，布洛芬抑制基础RhoA活性（Zhou等人，2003年）。最近的报道表明布洛芬促进脊髓损伤后皮质脊髓轴突再生（Fu et al.，2007年）。在这里，我们证实，布洛芬减少配体诱导的Rho信号和髓鞘诱导的抑制神经突起生长在体外。在脊髓挫伤后3天开始皮下给予布洛芬4周后，动物在更大程度上恢复了行走功能，有两倍多的大鼠达到后肢承重状态。我们研究了布洛芬作用中组织保留、轴突发芽和轴突再生的相对作用。在组织学上，布洛芬处理的动物显示备用组织增加，而星形胶质细胞或小胶质细胞反应没有改变。在损伤的脊髓中，Icadine增加了从肾上腺素能中缝脊神经轴突和从头侧皮质脊髓纤维的轴突发芽，但不允许脊髓挫伤后的尾侧皮质脊髓再生。对脊髓完全横断的小鼠的治疗表明，在布洛芬的存在下，长距离的中缝脊髓轴突再生。因此，布洛芬的给药通过保护组织、刺激轴突发芽和允许较小程度的中缝脊髓再生来改善大鼠从临床相关的脊髓创伤中的恢复。
The GTP-binding protein RhoA regulates microfilament dynamics in many cell types and mediates the inhibition of axonal regeneration by myelin and chondroitin sulfate proteoglycans. Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al., 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al., 2007). Here, we confirm that ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro. Following 4 weeks of subcutaneous administration of ibuprofen, beginning 3 days after spinal cord contusion, animals recovered walking function to a greater degree, with twice as many rats achieving a hind limb weight-bearing status. We examined the relative role of tissue sparing, axonal sprouting, and axonal regeneration in the action of ibuprofen. Histologically, ibuprofen-treated animals display an increase in spared tissue without an alteration in astrocytic or microglial reaction. Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal fibers in the injured spinal cord, but does not permit caudal corticospinal regeneration after spinal contusion. Treatment of mice with complete spinal cord transection demonstrates long-distance raphespinal axon regeneration in the presence of ibuprofen. Thus, administration of ibuprofen improves the recovery of rats from a clinically relevant spinal cord trauma by protecting tissue, stimulating axonal sprouting, and allowing a minor degree of raphespinal regeneration.