A dose-dependent facilitation and inhibition of peripheral nerve regeneration by brain-derived neurotrophic factor
A dose-dependent facilitation and inhibition of peripheral nerve regeneration by brain-derived neurotrophic factor
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DOI：
10.1046/j.1460-9568.2002.01891.x
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Gordon, T
中科院分区：
文献类型：
--
作者：
Boyd, JG;Gordon, T
轴突切除术后运动神经元再生轴突的能力随时间的下降是周围神经损伤后功能恢复不良的主要原因之一。神经营养支持的下降可能是造成这种影响的部分原因。损伤后 BDNF 在去神经雪旺细胞和轴突运动神经元中的上调表明其在运动轴突再生中的重要性。在成年雌性 Sprague-Dawley 大鼠中，我们计算了新受伤或慢性轴突切除的胫骨运动神经元的数量，这些运动神经元在手术缝合到新近去神经的腓总远端神经残端后 1 个月已再生轴突。通过将荧光逆行神经示踪剂应用于损伤部位远端 20 mm 的腓总神经，并计算脊髓 T-11-L-1 区域中荧光标记的运动神经元的数量来评估运动轴突再生。我们报道，低剂量的BDNF（0.5-2杯/天，持续28天）对立即神经修复后的轴突再生没有可检测到的影响，但促进了神经缝合前2个月因慢性轴突切断术而降低再生能力的运动神经元的轴突再生，完全逆转了延迟神经修复的负面影响。相比之下，在即刻神经修复和慢性轴突切除术后神经修复后，高剂量的 BDNF（12-20 杯/天，持续 28 天）显着抑制运动轴突再生。高剂量 BDNF 的抑制作用可以通过 p75 受体的功能性阻断来逆转，因此表明这些受体是高剂量外源 BDNF 抑制作用的介质。
The time-dependent decline in the ability of motoneurons to regenerate their axons after axotomy is one of the principle contributing factors to poor functional recovery after peripheral nerve injury. A decline in neurotrophic support may be partially responsible for this effect. The up-regulation of BDNF after injury, both in denervated Schwann cells and in axotomized motoneurons, suggests its importance in motor axonal regeneration. In adult female Sprague-Dawley rats, we counted the number of freshly injured or chronically axotomized tibial motoneurons that had regenerated their axons 1 month after surgical suture to a freshly denervated common peroneal distal nerve stump. Motor axonal regeneration was evaluated by applying fluorescent retrograde neurotracers to the common peroneal nerve 20 mm distal to the injury site and counting the number of fluorescently labelled motoneurons in the T-11-L-1 region of the spinal cord. We report that low doses of BDNF (0.5-2 mug/day for 28 days) had no detectable effect on axonal regeneration after immediate nerve repair, but promoted axonal regeneration of motoneurons whose regenerative capacity was reduced by chronic axotomy 2 months prior to nerve resuture, completely reversing the negative effects of delayed nerve repair. In contrast, high doses of BDNF (12-20 mug/day for 28 days) significantly inhibited motor axonal regeneration, after both immediate nerve repair and nerve repair after chronic axotomy. The inhibitory actions of high dose BDNF could be reversed by functional blockade of p75 receptors, thus implicating these receptors as mediators of the inhibitory effects of high dose exogenous BDNF.