King V R, Phillips J B, Brown R A, Priestley J V
Department of Neuroscience, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary College, University of London, Mile End Road, London E1 4NS, UK.
Neuroscience. 2004;126(1):173-83. doi: 10.1016/j.neuroscience.2004.03.035.
We recently showed axonal ingrowth into fibronectin (FN) mats implanted into the spinal cord. However, little axonal growth was found from FN mats into intact spinal cord. Previous research has shown that this is due in part to astrocytosis around an area of CNS damage. Antibodies to transforming growth factor beta (TGFbeta) can diminish this astrocytosis. TGFbeta also has effects on macrophages and Schwann cells, both of which infiltrate the spinal cord following damage. We examined the axonal, Schwann cell, and macrophage infiltration into FN mats as well as the level of astrocytosis and chondroitin sulfate proteoglycan NG2 around FN implants incubated in TGFbeta antibodies and implanted into a lesion cavity in the spinal cord. We also examined the effects of applying TGFbeta antibodies to a spinal cord hemisection site. Anti-TGFbeta1 within FN mats resulted in extensive cavitation, with the area of damage being larger than the original lesion. Cavitation was also seen following application of anti-TGFbeta1 to a spinal cord hemisection site. No cavitation was seen following saline, non-immune IgG or anti-TGFbeta2 treatment. However, anti-TGFbeta2 treatment did result in diminished axonal growth and Schwann cell and macrophage infiltration. Around the implant site, anti-TGFbeta2 treatment resulted in a reduction in the level of astrocytosis but had not effect on levels of NG2. Similar effects were seen following anti-TGFbeta2 application to spinal cord hemisection sites. The results suggest that anti-TGFbeta1 exacerbates secondary damage by preventing the anti-inflammatory effect of endogenous TGFbeta1. Anti-TGFbeta2 did not enhance axonal regeneration in this model but did slightly reduce astrocytosis.
我们最近发现轴突向内生长进入植入脊髓的纤连蛋白（FN）垫。然而，从FN垫向完整脊髓的轴突生长很少。先前的研究表明，这部分是由于中枢神经系统损伤区域周围的星形细胞增生。转化生长因子β（TGFβ）抗体可减少这种星形细胞增生。TGFβ对巨噬细胞和雪旺细胞也有作用，这两种细胞在损伤后都会浸润脊髓。我们研究了轴突、雪旺细胞和巨噬细胞向FN垫的浸润情况，以及在TGFβ抗体中孵育并植入脊髓损伤腔的FN植入物周围的星形细胞增生水平和硫酸软骨素蛋白聚糖NG2水平。我们还研究了将TGFβ抗体应用于脊髓半切部位的效果。FN垫内的抗TGFβ1导致广泛的空洞形成，损伤面积大于原始损伤。在脊髓半切部位应用抗TGFβ1后也出现了空洞形成。生理盐水、非免疫IgG或抗TGFβ2处理后未观察到空洞形成。然而，抗TGFβ2处理确实导致轴突生长减少以及雪旺细胞和巨噬细胞浸润减少。在植入部位周围，抗TGFβ2处理导致星形细胞增生水平降低，但对NG2水平没有影响。在脊髓半切部位应用抗TGFβ2后也观察到类似效果。结果表明，抗TGFβ1通过阻止内源性TGFβ1的抗炎作用而加剧继发性损伤。在该模型中，抗TGFβ2并未增强轴突再生，但确实略微减少了星形细胞增生。
