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首页> 外文期刊>The European Journal of Neuroscience >Inhibition of collagen IV deposition promotes regeneration of injured CNS axons.
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Inhibition of collagen IV deposition promotes regeneration of injured CNS axons.

机译:胶原蛋白IV沉积的抑制促进受伤的中枢神经系统轴突的再生。

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摘要

Scarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or alpha, alpha'-dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion-induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion-induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.
机译:瘢痕形成阻碍了轴突在整个病变部位的再生,并且是成年哺乳动物中枢神经系统有效再生的主要外在制约因素。在本研究中,我们确定了瘢痕的一个主要成分,基底膜(BM)的特异性生化或免疫化学调节是否将提供一种刺激成年大鼠的机械横断合后穹ni的轴突再生的方法。在横切后的前两周内,基膜发达,并与自然生长的轴突突然停止生长。局部注射抗胶原IV抗体或α,α'-联吡啶(一种胶原三螺旋结构的形成和合成抑制剂)可显着减少病变引起的BM沉积。该治疗使整个轴突在病变部位大量伸长。顺行性示踪提供了明确的证据,即再生轴突遵循其原始途径,重新激活了合适的靶标(即乳突体),并被致密的髓磷脂重新髓鞘化。再生纤维束的突触前电生理记录显示恢复到接近正常的传导特性。我们的结果表明,病变诱导的BM是成功完成轴突再生的障碍,而其减少是再生轴突穿过病变部位的前提和充分条件。

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