Resumo

Spinal cord injury (SCI) can lead to paraplegia or quadriplegia and it has a significant impact on quality of life, life expectancy and economic burden. Although there is no effective treatment for SCI, various rehabilitative, cellular and molecular therapies are currently under investigation in animal models. Laminin is an extracellular matrix protein implicated in neural development and regeneration. We have previously described that pH acidification leads to the formation of biomimetic polymers of laminin, which are able to restore the neuritogenic potential of mature neurons isolated from rat cerebral cortex and to promote axonal growth and tissue preservation after experimental SCI. Physical activity (exercise) and social and environmental enrichment (SEE) have been proposed as promising components of combination strategies for SCI, probably due to their capacity of actively engaging the patient in the recovering process. The aim of this study is to investigate the possible therapeutic benefits of cobining acid-polymerized laminin with SEE to treat experimental SCI. Rats were submitted to moderate compression, partial section or complete transection and the effects of treating them with laminin diluted either in a standard-neutral buffer (Bu 7; LM7) or in acidic buffer (Bu 4.0; LM4) were compared. Animals received acute treatment and were accompanied for two months, during which the open field locomotion test BBB was performed once per week. At the end of this period, the animals were perfused and the spinal tissue harvest to post-mortem assays to analyze the glial scar, tissue preservation and axonal regeneration. In rats submitted to compression and treated with LM7 there was no change in the course of the spontaneous functional recovery in comparison to control animals that received buffer only, either at pH 7 (Bu7) or at pH 4 (Bu4). On the other hand, animals treated with LM4 showed significantly higher BBB scores since the first week and throughout the evaluation period. The animals exposed to SEE significantly increased their BBB scores in all time points, the overall improvement fluctuating around 50% in comparison with the standard house group (p<0.05). When we compared the SEE plus acidic laminin group and standard house plus acidic laminin, we did not observed statistically significant differences (p>0.05). After complete transection the functional recovery observed for LM4-treated animals was more than 100% higher than that found in control groups. These findings show that LM4 alone injected acutely after SCI is capable of promoting recovery in different injury models. Similarly, SEE alone leads to functional benefits. It remains to be determined whether and by which means the combination of SEE and LM4 will be able to additionally improve functional recovery after SCI.