UP-REGULATION OF GAP-43 AND GROWTH OF AXONS IN RAT SPINAL-CORD AFTER COMPRESSION INJURY
UP-REGULATION OF GAP-43 AND GROWTH OF AXONS IN RAT SPINAL-CORD AFTER COMPRESSION INJURY
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DOI：
10.1007/bf01183975
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发表时间：
1993-01-01
期刊：
影响因子：
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通讯作者：
WILKIN, GP
中科院分区：
文献类型：
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作者：
CURTIS, R;GREEN, D;WILKIN, GP
生长相关蛋白43 （growth-associated protein-43, GAP-43）是一种轴突磷酸化蛋白，在发育过程中高水平表达，并在PNS再生过程中被重新诱导。因此，它被认为是调节轴突生长的关键分子。然而，中枢神经系统的损伤不会导致显著的再生，这被认为与轴截术后中枢神经元未能上调GAP-43有关。我们研究了一个脊髓损伤模型，它在两个方面是独特的；首先，通过平滑钳压迫脊髓（从而排除结缔组织成分）来保持硬脑膜的完整性，其次，据报道，通过由此产生的病变，有相当大的轴突生长。我们之前的研究表明，GAP-43在大鼠脊髓中广泛分布（见随附论文），但这里我们使用的是稀释后的抗GAP-43抗血清，在正常脊髓中没有产生任何免疫染色。然而，在压缩损伤后4天内，在病变周围的细胞体和轴突中检测到异常水平的GAP-43。RT97单克隆抗体的双重免疫染色表明，压迫部位局部的一小群神经元被无痛切除，并在其细胞体中表达GAP-43和磷酸化的神经丝表位。虽然长轴突束损伤广泛，但没有再生的证据。在白质中。另一方面，在灰质中形成的空腔为轴突伸长提供了环境。利用星形胶质细胞和内皮细胞标记物进行免疫标记，评估延长轴突与内源性中枢神经系统细胞类型的相互作用。萌芽轴突，通过存在高水平的GAP-43来识别，似乎不与星形胶质细胞接触生长，但初步证据表明，新形成的毛细血管提供了合适的基质。
The growth-associated protein-43 (GAP-43) is an axonal phosphoprotein which is expressed at high levels during development and is reinduced by regeneration in the PNS. Consequently it is believed to be a key molecule in the regulation of axonal growth. However, injury to the CNS does not result in significant regeneration and this has been suggested to correlate with a failure of central neurons to up-regulate GAP-43 after axotomy. We have examined a model of spinal cord injury which is unique in two respects; first dural integrity is maintained by compression of the cord with smooth forceps (thus excluding connective tissue elements) and, secondly, considerable axonal growth has been reported through the resulting lesion. Our previous studies have shown that GAP-43 is extensively distributed in the rat spinal cord (see accompanying paper), but here we have used anti-GAP-43 antiserum at a dilution which did not yield any immunostaining in normal cord. However, supranormal levels of GAP-43 were detected in cell bodies and axons around the lesion within four days of compression injury. Double immunostaining with the RT97 monoclonal antibody indicated that a small subpopulation of neurons local to the site of compression were axotomized and expressed GAP-43 and phosphorylated neurofilament epitopes in their cell bodies. Although damage to long axon tracts was extensive, there was no evidence of regeneration.in white matter. On the other hand cavities which formed in grey matter provided an environment for axonal elongation. Immunolabelling with markers for astrocytes and endothelial cells was used to evaluate the interaction of elongating axons with endogenous CNS cell types. Sprouting axons, idenfified by the presence of elevated levels of GAP-43, did not appear to grow in contact with astrocytes but preliminary evidence suggested that newly formed capillaries provided an appropriate substrate.