Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury

被引:33
作者
Menezes, Karla [1 ]
Lacerda de Menezes, Joao Ricardo [1 ]
Nascimento, Marcos Assis [1 ]
Santos, Raphael de Siqueira [1 ]
Coelho-Sampaio, Tatiana [1 ]
机构
[1] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Ctr Ciencias Saude, BR-21941590 Rio De Janeiro, Brazil
关键词
CNS regeneration; neuroprotection; protein polymerization; NECROSIS-FACTOR-ALPHA; BASEMENT-MEMBRANE; FUNCTIONAL RECOVERY; AXON REGENERATION; CNS; ADULT; INFLAMMATION; TRANSECTION; STRATEGIES; MATRICES;
D O I
10.1096/fj.10-157628
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regeneration of spinal cord injury (SCI) is a major topic of biomedical research. Laminin is an extracellular matrix protein implicated in neural development and regeneration, but despite that, there are no reports of exogenous laminin contributing to improve the outcome of experimental SCI. Here we investigated whether a biomimetic polymer of laminin assembled on pH acidification, henceforth called polylaminin, could be used to treat SCI in rats. Acute local injection of polylaminin, but not of nonpolymerized laminin, improved motor function after thoracic compression, partial or complete transection. In the latter case, the BBB score for open field locomotion 8 wk after lesion increased from 4.2 +/- 0.48 to 8.8 +/- 1.14 in animals treated with polylaminin of human origin. Accordingly, neurons retrogradely labeled from the sublesion stump were detected in the spinal cord and brain stem, indicating regrowth of short and long fibers across a complete transection. Polylaminin also played an unsuspected anti-inflammatory role, which underlies the early onset of its positive effects on locomotion from the first week after treatment. The beneficial effects of polylaminin were not observed in animals treated with the nonpolymerized protein or vehicle only. We propose that polylaminin is a promising therapeutic agent to treat human SCI.-Menezes, K., Menezes, J. R. L., Nascimento, M. A., Siqueira Santos, R., Coelho-Sampaio, T. Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury. FASEB J. 24, 4513-4522 (2010). www.fasebj.org
引用
收藏
页码:4513 / 4522
页数:10
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