Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.
Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury.
复制标题
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
复制
发表时间：
2006-10-18
期刊：
影响因子：
--
通讯作者：
Bradbury EJ
中科院分区：
文献类型：
--
作者：
Barritt AW;Davies M;Marchand F;Hartley R;Grist J;Yip P;McMahon SB;Bradbury EJ
硫酸软骨素蛋白聚糖（CSPG）是在CNS损伤后上调的抑制性细胞外基质分子。使用软骨素酶ABC（ChABC）降解CSPG可以促进脊髓损伤后的功能恢复。然而，这种复苏背后的机制尚不清楚。在这里，我们研究了ChABC治疗对促进脊髓内可塑性的影响。我们发现强大的发芽受伤（皮质脊髓）和完整的（肾上腺素能）下降的预测，以及未受伤的初级传入后，颈椎背柱损伤和ChABC治疗。在CSPG降解的区域中，在损伤近端的退化白色物质中的异常位置观察到发芽纤维。在脊髓灰质和病变水平以下也观察到皮质脊髓和肾上腺素能发芽纤维，表明对运动重要的下行投射末端区域的神经支配增加。用载体溶液处理的脊髓损伤动物未显示出显著的发芽。有趣的是，ChABC治疗未受伤的动物没有诱导发芽在任何系统。因此，去神经支配和CSPG降解都需要促进脊髓内的发芽。我们还研究了ChABC诱导的可塑性的潜在有害影响。然而，虽然初级传入发芽后观察到腰椎背柱病变和ChABC治疗，有没有增加的伤害性神经元的连接或机械异常性疼痛或热痛觉过敏的发展。因此，CSPG消化促进脊髓退化和失神经区域的脊髓投射的稳健发芽;这可能是功能恢复的关键机制。
Chondroitin sulphate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC treatment on promoting plasticity within the spinal cord. We found robust sprouting of both injured (corticospinal) and intact (serotonergic) descending projections as well as uninjured primary afferents following a cervical dorsal column injury and ChABC treatment. Sprouting fibres were observed in aberrant locations in degenerating white matter proximal to the injury in regions where CSPGs had been degraded. Corticospinal and serotonergic sprouting fibres were also observed in spinal grey matter at and below the level of the lesion, indicating increased innervation in the terminal regions of descending projections important for locomotion. Spinal injured animals treated with a vehicle solution showed no significant sprouting. Interestingly, ChABC treatment in uninjured animals did not induce sprouting in any system. Thus, both denervation and CSPG degradation were required to promote sprouting within the spinal cord. We also examined potential detrimental effects of ChABC-induced plasticity. However, while primary afferent sprouting was observed after lumbar dorsal column lesions and ChABC treatment, there was no increased connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia. Thus, CSPG digestion promotes robust sprouting of spinal projections in degenerating and denervated areas of the spinal cord; this could be a key mechanism underlying functional recovery.