Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E12AT, UK.
Neuroscience. 2010 Jun 30;168(2):523-30. doi: 10.1016/j.neuroscience.2010.03.040. Epub 2010 Mar 25.
We have shown previously that mats made from the glycoprotein fibronectin are permissive for axonal growth when implanted into the injured spinal cord. Recent evidence has indicated that fibronectin and its peptides also have neuroprotective effects in the CNS. We have therefore examined the neuroprotective effects of fibronectin applied to a spinal cord injury site. Adult rats with fibronectin mats implanted into a spinal cord lesion cavity had decreased apoptosis in the intact adjoining spinal cord tissue at 1 and 3 days post-injury compared to rats that had gelfoam implanted into the lesion cavity. Rats with fibronectin mat implants also showed enhanced hindlimb locomotor performance for the first 3 weeks post-surgery compared to control animals. To further examine the neuroprotective potential of fibronectin following spinal cord injury, we examined the effects of placing fibronectin mats over the site of a spinal cord hemisection or of delivering a solution derived from a dissolved fibronectin mat. The effects of these treatments were compared with control animals and animals that were treated with a fibronectin peptide (PRARIY) that has been shown to decrease secondary damage in a rodent model of cerebral ischemia. Results showed that both types of fibronectin mat treatment resulted in decreased lesion size, apoptosis, and axonal damage within the first week post-injury compared to control animals and were comparable in their neuroprotective efficacy to treatment with the fibronectin peptide. The results of the current study indicate that fibronectin based biomaterials have neuroprotective effects following spinal cord injury, in addition to their previously reported ability to promote axonal regeneration.
我们之前已经证明，植入损伤脊髓的纤维连接蛋白糖蛋白制成的基质允许轴突生长。最近的证据表明，纤维连接蛋白及其肽在中枢神经系统中也具有神经保护作用。因此，我们研究了纤维连接蛋白在脊髓损伤部位的神经保护作用。与植入凝胶海绵到损伤腔的大鼠相比，在损伤后 1 天和 3 天，将纤维连接蛋白基质植入脊髓损伤腔的成年大鼠的完整相邻脊髓组织中的细胞凋亡减少。与对照动物相比，植入纤维连接蛋白基质的大鼠在手术后的前 3 周也表现出更强的后肢运动表现。为了进一步研究脊髓损伤后纤维连接蛋白的神经保护潜力，我们检查了将纤维连接蛋白基质置于脊髓半切部位或输送源自溶解纤维连接蛋白基质的溶液的效果。将这些治疗方法的效果与对照动物和用已显示可减少啮齿动物脑缺血模型中继发性损伤的纤维连接蛋白肽（PRARIY）治疗的动物进行了比较。结果表明，与对照动物相比，这两种类型的纤维连接蛋白基质治疗在损伤后第一周内均导致损伤体积减小、细胞凋亡减少和轴突损伤减少，并且与用纤维连接蛋白肽治疗的效果相当。目前研究的结果表明，纤维连接蛋白基生物材料在脊髓损伤后具有神经保护作用，除了它们以前报道的促进轴突再生的能力。
